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Effects of Qilong Capsules on myocardial fibrosis and insufficient blood circulation in ischemic cardiomyopathy with Qi deficiency and blood stasis

Protección miocárdica - Lun, 03/28/2022 - 10:00

Zhongguo Zhong Yao Za Zhi. 2022 Mar;47(5):1327-1335. doi: 10.19540/j.cnki.cjcmm.20211216.701.


Protective effect of Qilong Capsules(QL) on the myocardial fibrosis and blood circulation of rats with coronary heart disease of Qi deficiency and blood stasis type was investigated. Sleep deprivation and coronary artery ligation were used to construct a disease-symptom combination model, and 60 SD rats were divided into sham operation(sham) group, syndrome(S) group, disease and syndrome(M) group and QL group randomly. The treatment group received administration of QL 0.4 g·kg~(-1)·d~(-1). Other groups were given the same amount of normal saline. The disease indexes of each group [left ventricular end diastolic diameter(LVESD), left ventricular end systolic diameter(LVEDD), left ventricular ejection fraction(LVEF), left ventricular axis shortening rate(LVFS), myocardial histopathology, platelet morphology, peripheral blood flow] and syndrome indexes(tongue color, pulse, grip power) were detected. In sham group, cardiomyocytes and myocardial fibers were arranged neatly and densely with clear structures. The tongues' color in sham were light red, and the pulse shape were regular. RGB is a parameter reflected the brightness of the image of the tongue. In the S group, the amplitude and frequency of the animal's pulse increased accompanied by decreasing R,G,B, however, the decreased R,G,B was accompanied by reduced pulse amplitude in M group. And in M group, we observed fuzzy cell morphology, hypertrophied myocytes, disordered arrangement of cardiomyocytes and myocardial fibers, reduced peripheral blood flow and increased collagen volume fraction(CVF). Increased LVESD and LVEDD, and decreased LVEF and LVFS represented cardiac function in S group was significantly lower than that in sham. In QL group, the tongue's color was red and the pulse was smooth. The myocardial fibers of the QL group were arranged neatly and secreted less collagen. It improved the blood circulation in the sole and tail, and reversed the increasing of LVEDD, LVESD and the decreasing of LVEF and LVFS of M group. Platelets in M and S group showed high reactivity, and QL could decrease aggregation risk. In conclusion, Qilong Capsules has an obvious myocardial protective effect on ischemic cardiomyopathy, which may inhibit the degree of myocardial fibrosis and reduce platelet reactivity.

PMID:35343161 | DOI:10.19540/j.cnki.cjcmm.20211216.701

Acacetin attenuates diabetes-induced cardiomyopathy by inhibiting oxidative stress and energy metabolism via PPAR-α/AMPK pathway

Protección miocárdica - Lun, 03/28/2022 - 10:00

Eur J Pharmacol. 2022 Mar 24:174916. doi: 10.1016/j.ejphar.2022.174916. Online ahead of print.


Diabetic cardiomyopathy seriously affects the life quality of diabetic patients and can lead to heart failure and death in severe cases. Acacetin was reported to be an anti-oxidant and anti-inflammatory agent in several cardiovascular diseases. However, the effect of acacetin on diabetic cardiomyopathy was not understood. This study was designed to explore the therapeutic effect of acacetin on diabetic cardiomyopathy and the potential mechanism with in vitro and in vivo experimental techniques. In cultured neonatal rat cardiomyocytes and H9C2 cardiac cells, acacetin (0.3, 1, 3 μM) showed effective protection against high glucose-induced injury in a concentration-dependent manner. Acacetin countered high glucose-induced increase of Bax and decrease of Bcl-2, SOD1, and SOD2. In streptozotocin-induced rat diabetic cardiomyopathy model, treatment with acacetin prodrug (10 mg/kg, s.c., b.i.d.) significantly improved the cardiac function and reduced myocardial injury, and reversed the increase of serum MDA, Ang Ⅱ, and IL-6 levels and myocardial Bax and IL-6, and the decrease of serum SOD, indicating that acacetin plays a cardioprotective effect by inhibiting oxidative stress, inflammation, and apoptosis. In addition, both in vitro and in vivo experimental results showed that acacetin increased the expression of PPAR-α and pAMPK, indicating that PPAR-α and pAMPK are potential targets of acacetin for the protection against diabetic cardiomyopathy. This study demonstrates the new application of acacetin for treating diabetic cardiomyopathy.

PMID:35341782 | DOI:10.1016/j.ejphar.2022.174916

Ketone Body beta-Hydroxybutyrate Prevents Myocardial Oxidative Stress in Septic Cardiomyopathy

Protección miocárdica - Lun, 03/28/2022 - 10:00

Oxid Med Cell Longev. 2022 Mar 18;2022:2513837. doi: 10.1155/2022/2513837. eCollection 2022.


Septic cardiomyopathy is a life-threatening complication of severe sepsis and septic shock. Oxidative stress and mitochondrial dysfunction have been identified as significant abnormalities in septic cardiomyopathy. However, specific treatments are rare. This study aims to investigate the impact of β-hydroxybutyrate (β-OHB) on septic cardiomyopathy and explore the underlying mechanism(s). We found that pretreatment of D-β-hydroxybutyrate-(R)-1,3 butanediol monoester (ketone ester, 3 mg/g body weight, once daily) by gavage for three days elevated the levels of ketone bodies, especially that of β-hydroxybutyrate (β-OHB) in the circulation and mouse hearts, which exerted a protective effect against lipopolysaccharide (LPS, 20 mg/kg)-induced septic cardiomyopathy in mice. In addition, an LPS-stimulated macrophage-conditioned medium (MCM) was used to mimic the pathological process of septic cardiomyopathy. Mechanistically, β-OHB alleviated myocardial oxidative stress and improved mitochondrial respiratory function through the antioxidant FoxO3a/MT2 pathway activated via histone deacetylase (HDAC) inhibition, which ultimately enhanced heart performance in septic cardiomyopathy. Our results, therefore, suggested an unappreciated critical role of β-OHB in septic heart protection as well as highlighted the potential of β-OHB as a simple remedy for the septic cardiomyopathy population.

PMID:35340211 | PMC:PMC8956399 | DOI:10.1155/2022/2513837

Chinese expert consensus on microvascular protection strategy during emergency PCI therapy in patients with ST-elevation myocardial infarction

Protección miocárdica - Dom, 03/27/2022 - 10:00

Zhonghua Xin Xue Guan Bing Za Zhi. 2022 Mar 24;50(3):221-230. doi: 10.3760/cma.j.cn112148-20211112-00987.


PMID:35340140 | DOI:10.3760/cma.j.cn112148-20211112-00987

UCHL1 protects against ischemic heart injury via activating HIF-1alpha signal pathway

Protección miocárdica - Dom, 03/27/2022 - 10:00

Redox Biol. 2022 Mar 18;52:102295. doi: 10.1016/j.redox.2022.102295. Online ahead of print.


Ubiquitin carboxyl-terminal esterase L1 (UCHL1) has been thought to be a neuron specific protein and shown to play critical roles in Parkinson's Disease and stroke via de-ubiquiting and stabilizing key pathological proteins, such as α-synuclein. In the present study, we found that UCHL1 was significantly increased in both mouse and human cardiomyocytes following myocardial infarction (MI). When LDN-57444, a pharmacological inhibitor of UCHL1, was used to treat mice subjected to MI surgery, we found that administration of LDN-57444 compromised cardiac function when compared with vehicle treated hearts, suggesting a potential protective role of UCHL1 in response to MI. When UCHL1 was knockout by CRISPR/Cas 9 gene editing technique in human induced pluripotent stem cells (hiPSCs), we found that cardiomyocytes derived from UCHL1-/- hiPSCs were more susceptible to hypoxia/re-oxygenation induced injury as compared to wild type cardiomyocytes. To study the potential targets of UCHL1, a BioID based proximity labeling approach followed by mass spectrum analysis was performed. The result suggested that UCHL1 could bind to and stabilize HIF-1α following MI. Indeed, expression of HIF-1α was lower in UCHL1-/- cells as determined by Western blotting and HIF-1α target genes were also suppressed in UCHL1-/- cells as quantified by real time RT-PCR. Recombinant UCHL1 (rUCHL1) protein was purified by E. Coli fermentation and intraperitoneally (I.P.) delivered to mice. We found that administration of rUCHL1 could significantly preserve cardiac function following MI as compared to control group. Finally, adeno associated virus mediated cardiac specific UCHL1 delivery (AAV9-cTNT-m-UCHL1) was performed in neonatal mice. UCHL1 overexpressing hearts were more resistant to MI injury as compare to the hearts infected with control virus. In summary, our data revealed a novel protective role of UCHL1 on MI via stabilizing HIF-1α and promoting HIF-1α signaling.

PMID:35339825 | DOI:10.1016/j.redox.2022.102295

Implication of IGF1R signaling in the protective effect of Astragaloside IV on ischemia and reperfusion-induced cardiac microvascular endothelial hyperpermeability

Protección miocárdica - Sáb, 03/26/2022 - 10:00

Phytomedicine. 2022 Mar 13;100:154045. doi: 10.1016/j.phymed.2022.154045. Online ahead of print.


BACKGROUND: Myocardial ischemia-reperfusion (I/R) causes damage to coronary capillary endothelial barrier and microvascular leakage (MVL), aggravating tissue injury and heart dysfunction. However, the effective strategy for protecting endothelium barrier of cardiac vasculature remains limited.

PURPOSE: This study aimed to explore the effect of Astragaloside IV (ASIV) on coronary MVL after cardiac I/R and the underlying mechanism.

STUDY DESIGN: Sprague-Dawley (SD) rats were used for assessment of the efficacy of Astragaloside IV in protection of myocardial I/R injury, while human cardiac microvascular endothelial cells were applied to gain more insight into the underlying mechanism.

METHODS: Sprague-Dawley rats with or without pretreatment by ASIV at 10 mg/kg were subjected to occlusion of left coronary anterior descending artery followed by reperfusion. Endothelial cells were exposed to hypoxia and re-oxygenation (H/R). The distribution of junction proteins was detected by immunofluorescence staining and confocal microscope, the content of junction proteins was detected by Western blot, the level of adenosine triphosphate (ATP) was detected by ELISA, and the signal pathway related to permeability was detected by siRNA infection. The fluorescence intensity of FITC-albumin and FITC-Dextran was measured to evaluate the permeability of endothelial cells.

RESULTS: ASIV exhibited protective effects on capillary damage, myocardium edema, albumin leakage, leucocyte infiltration, and the downregulated expression of endothelial junction proteins after I/R. Moreover, ASIV displayed ability to protect ATP from depletion after I/R or H/R, and the effect of ASIV on regulating vascular permeability and junction proteins was abolished once ATP synthase was inhibited. Notably, ASIV activated the insulin-like growth factor 1 receptor (IGF1R) and downstream signaling after reoxygenation. Knocking IGF1R down abolished the effect of ASIV on restoration of ATP, junction proteins and endothelial barrier after H/R.

CONCLUSION: ASIV was potential to prevent MVL after I/R in heart. Moreover, the study for the first time demonstrated that the beneficial role of ASIV depended on promoting production of ATP through activating IGF1R signaling pathway. This result provided novel insight for better understanding the mechanism underlying the potential of ASIV to cope with cardiac I/R injury.

PMID:35338991 | DOI:10.1016/j.phymed.2022.154045

The histone demthylase KDM3A protects the myocardium from ischemia/reperfusion injury via promotion of ETS1 expression

Protección miocárdica - Sáb, 03/26/2022 - 10:00

Commun Biol. 2022 Mar 25;5(1):270. doi: 10.1038/s42003-022-03225-y.


Our prior studies have characterized the participation of histone demethylase KDM3A in diabetic vascular remodeling, while its roles in myocardial ischemia/reperfusion (I/R) injury (MIRI) remain to be illustrated. Here we show that KDM3A was significantly downregulated in rat I/R and cellular hypoxia/reoxygenation (H/R) models. Subsequently, gain- and loss-of-function experiments were performed to investigate the effects of KDM3A in the settings of MIRI. KDM3A knockout exacerbated cardiac dysfunction and cardiomyocytes injury both in vivo and in vitro. The deteriorated mitochondrial apoptosis, reactive oxygen species, and inflammation were simultaneously observed. Conversely, KDM3A overexpression developed the ameliorated alternations in MIRI. Mechanistically, the MIRI-alleviating effects of KDM3A were associated with the enhancement of ETS1 expression. ChIP-PCR affirmed that KDM3A bound to the ETS1 promoter and removed dimethylation of histone H3 lysine 9 (H3K9me2), thus promoting ETS1 transcription. Our findings suggest that KDM3A is available for alleviating multi-etiologies of MIRI through the regulation of ETS1.

PMID:35338235 | DOI:10.1038/s42003-022-03225-y

Baicalin promotes the activation of brown and white adipose tissue through AMPK/PGC1α pathway

Protección miocárdica - Sáb, 03/26/2022 - 10:00

Eur J Pharmacol. 2022 Mar 22:174913. doi: 10.1016/j.ejphar.2022.174913. Online ahead of print.


Obesity occurs when energy intake overtops energy expenditure. Promoting activation of brown adipose tissue (BAT) and white adipose tissue (WAT) has been proven a promising therapeutic strategy for obesity. Baicalin (BAI) has been shown to be protective for various animal models of cardiovascular diseases, such as pulmonary hypertension, atherosclerosis and myocardial hypertrophy. However, whether BAI could stimulate activation of BAT or browning of WAT remains unknown. Here we show that BAI limits weight gaining, ameliorates glucose tolerance, improves cold tolerance and promotes brown-like tissue formation in diet induced obesity mice model. BAI increases the mitochondrial copy number as judged by mtDNA detection. BAI also increases the expression of UCP1 and other classical browning-specific genes in BAT and WAT and cultured C3H10T1/2 adipocytes through a mechanism involving AMPK/PGC1α pathway. Collectively, our study established a role for BAI in regulating energy metabolism, which will provide new idea and theoretical basis for the treatment of obesity.

PMID:35337814 | DOI:10.1016/j.ejphar.2022.174913

New Synthetic Analogues of Natural Polyphenols as Sirtuin 1-Activating Compounds

Protección miocárdica - Sáb, 03/26/2022 - 10:00

Pharmaceuticals (Basel). 2022 Mar 10;15(3):339. doi: 10.3390/ph15030339.


NAD+-dependent deacetylase SIRT1 regulates many different biological processes, thus being involved in pathogenic conditions such as metabolic diseases, neurogenerative disorders and cancer. Notably, experimental evidence underlined that the activation of SIRT1 had promising cardioprotective effects. Consequently, many efforts have been so far devoted to finding new SIRT1 activators, both derived from natural sources or prepared by synthetic procedures. Herein, we discovered new SIRT1-activating derivatives, characterized by phenolic rings spaced by sulfur, nitrogen or oxygen-based central linkers. The newly synthesized derivatives were analyzed in enzymatic assays to determine their ability to activate SIRT1, as compared with that of resveratrol. Among the tested molecules, bisarylaniline compound 10 proved to be the most efficient SIRT1 activator. An evaluation of the effects caused by focused structural variations revealed that its para-hydroxy-substituted diphenyl moiety of 10 was the fundamental structural requirement for achieving good SIRT1 activation. Compound 10 was further investigated in ex vivo studies in isolated and perfused rat hearts submitted to ischemia/reperfusion (I/R), where it showed significant protection of the myocardium against I/R injury. Molecular modeling studies suggest the binding mode of 10 within SIRT1 in the presence of the p53-AMC peptide. Our findings reveal that this chemical scaffold may be used as the starting point to develop a new class of more potent SIRT1 activators as cardioprotective agents.

PMID:35337137 | PMC:PMC8949162 | DOI:10.3390/ph15030339

AMPK Activation Is Indispensable for the Protective Effects of Caloric Restriction on Left Ventricular Function in Postinfarct Myocardium

Protección miocárdica - Sáb, 03/26/2022 - 10:00

Biology (Basel). 2022 Mar 16;11(3):448. doi: 10.3390/biology11030448.


BACKGROUND: Caloric restriction (CR) extends lifespan in many species, including mammals. CR is cardioprotective in senescent myocardium by correcting pre-existing mitochondrial dysfunction and apoptotic activation. Furthermore, it confers cardioprotection against acute ischemia-reperfusion injury. Here, we investigated the role of AMP-activated protein kinase (AMPK) in mediating the cardioprotective CR effects in failing, postinfarct myocardium.

METHODS: Ligation of the left coronary artery or sham operation was performed in rats and mice. Four weeks after surgery, left ventricular (LV) function was analyzed by echocardiography, and animals were assigned to different feeding groups (control diet or 40% CR, 8 weeks) as matched pairs. The role of AMPK was investigated with an AMPK inhibitor in rats or the use of alpha 2 AMPK knock-out mice.

RESULTS: CR resulted in a significant improvement in LV function, compared to postinfarct animals receiving control diet in both species. The improvement in LV function was accompanied by a reduction in serum BNP, decrease in LV proapoptotic activation, and increase in mitochondrial biogenesis in the LV. Inhibition or loss of AMPK prevented most of these changes.

CONCLUSIONS: The failing, postischemic heart is protected from progressive loss of LV systolic function by CR. AMPK activation is indispensable for these protective effects.

PMID:35336822 | PMC:PMC8945456 | DOI:10.3390/biology11030448

Role of Epicardial Adipose Tissue in Cardiovascular Diseases: A Review

Protección miocárdica - Sáb, 03/26/2022 - 10:00

Biology (Basel). 2022 Feb 23;11(3):355. doi: 10.3390/biology11030355.


Cardiovascular diseases (CVDs) are the leading causes of death worldwide. Epicardial adipose tissue (EAT) is defined as a fat depot localized between the myocardial surface and the visceral layer of the pericardium and is a type of visceral fat. EAT is one of the most important risk factors for atherosclerosis and cardiovascular events and a promising new therapeutic target in CVDs. In health conditions, EAT has a protective function, including protection against hypothermia or mechanical stress, providing myocardial energy supply from free fatty acid and release of adiponectin. In patients with obesity, metabolic syndrome, or diabetes mellitus, EAT becomes a deleterious tissue promoting the development of CVDs. Previously, we showed an adverse modulation of gene expression in pericoronary adipose tissue in patients with coronary artery disease (CAD). Here, we summarize the currently available evidence regarding the role of EAT in the development of CVDs, including CAD, heart failure, and atrial fibrillation. Due to the rapid development of the COVID-19 pandemic, we also discuss data regarding the association between EAT and the course of COVID-19. Finally, we present the potential therapeutic possibilities aiming at modifying EAT's function. The development of novel therapies specifically targeting EAT could revolutionize the prognosis in CVDs.

PMID:35336728 | PMC:PMC8945130 | DOI:10.3390/biology11030355

Cardiovascular efficacy of liraglutide and semaglutide in individuals with diabetes and peripheral artery disease

Protección miocárdica - Vie, 03/25/2022 - 10:00

Diabetes Obes Metab. 2022 Mar 24. doi: 10.1111/dom.14700. Online ahead of print.


AIMS: Patients with peripheral artery disease (PAD) and type 2 diabetes (T2D) are at heightened risk of cardiovascular (CV) events. This analysis evaluated the CV efficacy of liraglutide and semaglutide in patients with T2D and PAD.

MATERIALS AND METHODS: LEADER and SUSTAIN 6 trials investigated subcutaneous liraglutide (≤1.8 mg/day) and semaglutide (0.5 or 1.0 mg/week), respectively, versus placebo in patients with T2D and high CV risk (median follow-up: 3.8 and 2.1 years, respectively).

PRIMARY OUTCOME: composite of CV death, nonfatal myocardial infarction or nonfatal stroke (major adverse CV event [MACE]) according to presence of PAD at baseline.

RESULTS: Overall, 1184/9340 (12.7%) patients in LEADER and 460/3297 (14.0%) in SUSTAIN 6 had PAD at baseline. Patients with PAD were at ~35% increased risk of MACE versus those without (LEADER: hazard ratio [HR] 1.36, 95% confidence interval [CI] 1.17-1.58; SUSTAIN 6: HR 1.33, 95% CI 0.94-1.83). The effect of both therapies on MACE were consistently beneficial in patients with PAD (liraglutide: HR 0.77, 95% CI 0.58-1.01; semaglutide: 0.61, 0.33-1.13) and without (liraglutide: HR 0.89, 95% CI 0.79-1.00; semaglutide: HR 0.77, 95% CI 0.58-1.01; Pinteraction = 0.34 for liraglutide and 0.49 for semaglutide). Absolute risk reductions for MACE were higher in patients with PAD (liraglutide: 4.13 %-point, 95% CI -0.15-8.42; semaglutide: 4.63 %-point, 95% CI -0.58-9.84) vs without (liraglutide:1.42 %-point, 95% CI -0.03-2.87; semaglutide: 1.90 %-point, 95% CI 0.00-3.80).

CONCLUSIONS: Both liraglutide and semaglutide reduce MACE with consistent CV efficacy regardless of PAD status. This article is protected by copyright. All rights reserved.

PMID:35332654 | DOI:10.1111/dom.14700

Hesperidin protects against cisplatin-induced cardiotoxicity in mice by regulating the p62-Keap1-Nrf2 pathway

Protección miocárdica - Vie, 03/25/2022 - 10:00

Food Funct. 2022 Mar 24. doi: 10.1039/d2fo00298a. Online ahead of print.


Hesperidin (HES) is an abundant and economical dietary bioflavonoid, and it has several pharmacological properties such as antioxidant activity and powerful cardiac protection. However, HES protection against cisplatin (CP)-induced cardiotoxicity and its mechanism have not been fully clarified. The current study was performed to further elucidate the mechanism of HES against CP-induced cardiotoxicity. Mice were orally administered HES (100 or 300 mg kg-1 day-1) for 7 consecutive days and then injected intraperitoneally (i.p.) with CP (5 mg kg-1) on days 3 and 6. On day 8, mice were anaesthetised with sodium pentobarbital (50 mg kg-1, i.p.), and blood and heart samples were collected for analysis. HES treatment reduced CP-induced cardiac pathologic damage and leakage of the myocardial markers cardiac troponin I (cTnI), creatine kinase (CK), and lactate dehydrogenase (LDH). HES treatment reduced levels of reactive oxygen species (ROS) and malondialdehyde (MDA), which is an oxidative product, and increased antioxidant marker levels including superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). HES also reduced the CP-induced release of the inflammatory factors tumour necrosis factor (TNF)-α and interleukin (IL)-6. Additionally, HES treatment up-regulated the expression of anti-apoptotic protein Bcl-2 and down-regulated the expression of pro-apoptotic proteins Bax and Caspase-3. HES treatment also improved the expression of pathway proteins p62 and Nrf2 and inhibited the increase in CP-induced Keap1 expression. Thus, HES may provide protection against CP cardiotoxicity through inhibiting oxidative stress, inflammation, and apoptosis, which may contribute to activation of the p62-Keap1-Nrf2 signalling pathway. These findings suggest that HES may be a promising protective agent against CP cardiotoxicity in future anticancer clinical practice.

PMID:35332348 | DOI:10.1039/d2fo00298a

Smilax glabra Roxb. flavonoids protect against pathological cardiac hypertrophy by inhibiting the Raf/MEK/ERK pathway: In vivo and in vitro studies

Protección miocárdica - Vie, 03/25/2022 - 10:00

J Ethnopharmacol. 2022 Mar 21:115213. doi: 10.1016/j.jep.2022.115213. Online ahead of print.


ETHNOPHARMACOLOGICAL RELEVANCE: Smilax glabra Roxb., the dry rhizome of Sarsaparilla, which is also known as Tu fuling (TFL) in China, is a well-known traditional CHINESE medicine that is widely used for detoxication, relieving dampness and as a diuretic. We have previously shown that the extracted TFL flavonoids (designated TFLF) possess anti-cardiac hypertrophy effects in vitro. However, the anti-cardiac hypertrophy effects of TFLF in vivo and the underlying mechanisms remain to be elucidated.

AIM OF THE STUDY: To reveal the underlying therapeutic mechanism of TFLF on cardiac hypertrophy by using transverse aortic constriction (TAC) model and cellular assays in vitro.

MATERIAL & METHODS: Cardiac hypertrophy was replicated by TAC surgery in rats or by isoprenaline treatment of rat H9C2 myocardial cells in vitro. Cardiac structure and function were evaluated by echocardiographic and hemodynamic examinations in vivo and histological analysis of tissues ex vivo. Biochemical kits and quantitative PCR were used to analyze markers of cardiac hypertrophy. Expression and phosphorylation of key proteins in the Raf/MEK/ERK pathway were quantified by Western blotting. We further confirmed our findings in H9C2 rat cardiomyocytes treated with isoprenaline and the ERK inhibitor in vitro.

RESULTS: TFLF attenuated cardiac hypertrophy and fibrosis and improved cardiac dysfunction in TAC rats. TFLF treatment induced a strong reduction in serum NT-proBNP levels. Cardiac hypertrophy marker gene (ANP, BNP and β-MHC) expression and the phosphorylation levels of c-Raf and ERK1/2 were decreased by TFLF treatment. TFLF also protected H9C2 cells from isoprenaline-induced hypertrophy in vitro via a similar molecular mechanism as that observed in the rat heart. Moreover, pretreatment with TRLF and the ERK inhibitor further inhibited the mRNA overexpression of hypertrophic genes in vitro.

CONCLUSIONS: TFLFs may protect against pathological cardiac hypertrophy via negative regulation of the Raf/MEK/ERK pathway. Thus, TFLFs are implicated as a potential pharmacological agent for treating cardiac hypertrophy in clinical practice.

PMID:35331878 | DOI:10.1016/j.jep.2022.115213

Same-Day Discharge Post-Transcatheter Aortic Valve Replacement During the COVID-19 Pandemic: The Multicenter PROTECT TAVR Study

Protección miocárdica - Vie, 03/25/2022 - 10:00

JACC Cardiovasc Interv. 2022 Mar 28;15(6):590-598. doi: 10.1016/j.jcin.2021.12.046.


OBJECTIVES: The aim of this study was to determine the safety and efficacy of same-day discharge (SDD) after transcatheter aortic valve replacement (TAVR) during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has placed significant stress on health care systems worldwide. SDD in highly selected TAVR patients can facilitate the provision of essential cardiovascular care while managing competing COVID-19 resource demands.

METHODS: Patient selection for SDD was at the discretion of the local multidisciplinary heart team, across 7 international sites. The primary outcome was a composite of cardiovascular death, stroke, myocardial infarction, all-cause readmission, major vascular complications, and new permanent pacemaker (PPM) implantation.

RESULTS: From March 2020 to August 2021, 124 of 2,100 patients who underwent elective transfemoral TAVR were selected for SDD. The average age was 78.9 ± 7.8 years, the median Society of Thoracic Surgeons score was 2.4 (IQR: 1.4-4.2), and 32.3% (n = 40) had preexisting PPMs. There were no major vascular complications, strokes, or deaths during the index admission. One patient (0.8%) required PPM implantation for complete heart block and was discharged the same day. No patient required a PPM between discharge home and 30-day follow-up. The composite of cardiovascular death, stroke, myocardial infarction, all-cause readmission, major vascular complications, and new PPM at 30 days occurred in 5.7% patients (n = 6 of 106).

CONCLUSIONS: SDD post-TAVR is safe and feasible in selected patients at low risk for adverse clinical events postdischarge. This strategy may have a potential role in highly selected patients even when the COVID-19 pandemic abates.

PMID:35331450 | PMC:PMC8936029 | DOI:10.1016/j.jcin.2021.12.046

Estrogen inhibits endoplasmic reticulum stress and ameliorates myocardial ischemia/reperfusion injury in rats by upregulating SERCA2a

Protección miocárdica - Vie, 03/25/2022 - 10:00

Cell Commun Signal. 2022 Mar 24;20(1):38. doi: 10.1186/s12964-022-00842-2.


BACKGROUND: The incidence of coronary heart disease (CHD) in premenopausal women is significantly lower than that of men of the same age, suggesting protective roles of estrogen for the cardiovascular system against CHD. This study aimed to confirm the protective effect of estrogen on myocardium during myocardial ischemia/reperfusion (MI/R) injury and explore the underlying mechanisms.

METHODS: Neonatal rat cardiomyocytes and Sprague-Dawley rats were used in this study. Different groups were treated by bilateral ovariectomy, 17β-estradiol (E2), adenoviral infection, or siRNA transfection. The expression of sarcoplasmic reticulum Ca2+ ATPase pump (SERCA2a) and endoplasmic reticulum (ER) stress-related proteins were measured in each group to examine the effect of different E2 levels and determine the relationship between SERCA2a and ER stress. The cell apoptosis, myocardial infarction size, levels of apoptosis and serum cardiac troponin I, ejection fraction, calcium transient, and morphology changes of the myocardium and ER were examined to verify the effects of E2 on the myocardium.

RESULTS: Bilateral ovariectomy resulted in reduced SERCA2a levels and more severe MI/R injury. E2 treatment increased SERCA2a expression. Both E2 treatment and exogenous SERCA2a overexpression decreased levels of ER stress-related proteins and alleviated myocardial damage. In contrast, SERCA2a knockdown exacerbated ER stress and myocardial damage. Addition of E2 after SERCA2a knockdown did not effectively inhibit ER stress or reduce myocardial injury.

CONCLUSIONS: Our data demonstrate that estrogen inhibits ER stress and attenuates MI/R injury by upregulating SERCA2a. These results provide a new potential target for therapeutic intervention and drug discovery in CHD. Video Abstract.

PMID:35331264 | PMC:PMC8944077 | DOI:10.1186/s12964-022-00842-2

Meta-analysis of the association between Apolipoprotein E polymorphism and risks of myocardial infarction

Protección miocárdica - Vie, 03/25/2022 - 10:00

BMC Cardiovasc Disord. 2022 Mar 24;22(1):126. doi: 10.1186/s12872-022-02566-0.


BACKGROUND: Myocardial infarction (MI) remains the leading cause of death and disability among cardiovascular diseases worldwide. Studies show that elevated low-density lipid protein cholesterol (LDL-C) levels confer the highest absolute risk of MI, and Apolipoprotein E (ApoE) is implicated in regulating levels of triglycerides (TGs), cholesterol, and LDL-C. Our study aimed to evaluate the association between APOE polymorphism and MI, and to provide evidence for the etiology of MI.

METHODS: Case-control studies on the association between APOE polymorphisms and the risk of myocardial infarction were included by searching PubMed, Web of Science, and CNKI, and this meta-analysis was written in accordance with PRISMA guideline statement. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using either random-effects or fixed-effects models by R software.

RESULTS: A total of 33 eligible articles involving 13,706 cases and 14,817 controls were finally selected. The pooled analysis based on the total eligible articles showed that the risk of MI was associated with ApoE epsilon 2 and epsilon 4 alleles. The results showed that patients with MI had a low frequency of the ε2 allele (OR 0.74, 95% CI 0.64-0.86) and a high frequency of the ε4 allele (OR 1.24, 95% CI 1.09-1.42).

CONCLUSIONS: APOE ε2-involved genotypes may be protective factors for MI; in contrast, ε4-involved genotypes (ε4/ε3 vs. ε3/ε3, and ε4/ε4 vs. ε3/ε3) may be risk factors for MI.

PMID:35331149 | PMC:PMC8952226 | DOI:10.1186/s12872-022-02566-0

Percutaneous Coronary Intervention versus Coronary Artery Bypass Grafting for Non-Protected Left Main Coronary Artery Disease: 1-Year Outcomes in a High Volume Single Center Study

Protección miocárdica - Vie, 03/25/2022 - 10:00

Life (Basel). 2022 Feb 27;12(3):347. doi: 10.3390/life12030347.


INTRODUCTION: There is clear evidence of a significant reduction in all major cardiovascular adverse events (MACE) by coronary artery bypass grafting (CABG) in left main coronary artery stenosis (LMCS), but revascularization by percutaneous coronary artery intervention (PCI) shows an increasingly important role as an alternative to CABG. Several recent trials aiming to test the difference in mortality between the two types of revascularization found conflicting data. The aim of this study is to determine whether PCI is non-inferior to CABG with respect to the occurrence of MACE at 1 year in patients with significant LMCS.

MATERIAL AND METHODS: We prospectively enrolled 296 patients with chronic or acute coronary syndromes and significant LM stenosis. The angiography that recommended the revascularization procedure was used for the calculation of the Syntax II score, in order to classify the patients as low-, intermediate- or high-risk. Low- and high-risk patients were revascularized with either PCI or CABG, according to current guidelines, and were included in the subgroup S1. The second subgroup (S0) included intermediate-risk patients (Syntax II score 23-32), in whom the type of revascularization was chosen depending on the decision of the heart team or the patient preference. Patients were monitored according to the chosen mode of revascularization-PCI or CABG. LM revascularization was performed in all the patients. Clinical endpoints included cardiac death, myocardial infarction, need for revascularization and stroke. Patients were evaluated at 1 year after revascularization. Event rates were estimated using the Kaplan-Meier analysis in time to the first event.

RESULTS: At 1-year follow-up, a primary endpoint occurred in 35/95 patients in the CABG group and 37/201 in the PCI group. There were no significant differences between the 2 treatment strategies in the 1-year components of the end-point. However, a tendency to higher occurrence of cardiac death (HR = 1.48 CI (0.55-3.9), p = 0.43), necessity of repeat revascularization (HR = 1.7, CI (0.81-3.6), p = 0.16) and stroke (HR = 1.52, CI (1.15-2.93), p = 0.58) were present after CABG. Contrariwise, although without statistical significance, MI was more frequent after PCI (HR = 2, CI (0.78-5.2), p = 0.14). The Kaplan-Meier estimates in subgroups demonstrated the same tendency to higher rates for cardiac death, repeat revascularization and stroke after CABG, and higher rates of MI after PCI. Although without statistical significance, patients with an intermediate-risk showed a slightly lower risk of MACE after PCI than CABG. With the exception of dyslipidemia and gender, other cardiovascular risk factors were in favor of CABG (CKD, obesity).

CONCLUSION: In patients with LMCS, PCI with drug-eluting stents was non-inferior to CABG with respect to the composite of cardiac death, myocardial infarction, repeat revascularization and stroke at 1 year, even in patients with intermediate Syntax II risk score.

PMID:35330098 | PMC:PMC8953531 | DOI:10.3390/life12030347

Coronary Malperfusion Secondary to Acute Type A Aortic Dissection: Surgical Management Based on a Modified Neri Classification

Protección miocárdica - Vie, 03/25/2022 - 10:00

J Clin Med. 2022 Mar 18;11(6):1693. doi: 10.3390/jcm11061693.


BACKGROUND: Coronary malperfusion (CM) secondary to acute type A aortic dissection (ATAAD) is considered rare but has a high mortality rate. This study examined the incidence, management, and outcomes of patients with CM secondary to ATAAD and proposes a modified Neri classification.

METHODS: Between 2015 and 2020, out of 1018 patients who underwent surgical repair for ATAAD, 137 presented with CM, including 68 (49.6%), 43 (31.3%), and 15 (10.9%) with Neri types A, B, and C, respectively, and 11 (8.0%) with coronary orifice intimal tear (COIT), which we consider a novel category.

RESULTS: The occurrence rate of CM was 13.4%. CM was associated with higher in-hospital mortality (18.2% vs. 7.8%, p < 0.001). For Neri type A (98.5%) and most type B lesions (72.1%), coronary repair was adequate. Coronary artery bypass grafting (CABG) was necessary for type B patients unsuited for repair (23.2%) and for all type C patients (100%). Repair of COIT was possible (45.5%). The in-hospital mortality rates differed significantly among the four lesion groups (p = 0.006).

CONCLUSIONS: The occurrence of CM secondary to ATAAD may be more frequent than previously reported. Surgical management based on lesion classification achieved acceptable outcomes. Repair was adequate for Neri type A and most type B lesions. Other type B and type C lesions could be treated by CABG. Coronary orifice intimal tear is a unique set of lesions, for which orifice repair was also possible.

PMID:35330018 | PMC:PMC8949911 | DOI:10.3390/jcm11061693

Interconnection between Cardiac Cachexia and Heart Failure-Protective Role of Cardiac Obesity

Protección miocárdica - Vie, 03/25/2022 - 10:00

Cells. 2022 Mar 18;11(6):1039. doi: 10.3390/cells11061039.


Cachexia may be caused by congestive heart failure, and it is then called cardiac cachexia, which leads to increased morbidity and mortality. Cardiac cachexia also worsens skeletal muscle degradation. Cardiac cachexia is the loss of edema-free muscle mass with or without affecting fat tissue. It is mainly caused by a loss of balance between protein synthesis and degradation, or it may result from intestinal malabsorption. The loss of balance in protein synthesis and degradation may be the consequence of altered endocrine mediators such as insulin, insulin-like growth factor 1, leptin, ghrelin, melanocortin, growth hormone and neuropeptide Y. In contrast to many other health problems, fat accumulation in the heart is protective in this condition. Fat in the heart can be divided into epicardial, myocardial and cardiac steatosis. In this review, we describe and discuss these topics, pointing out the interconnection between heart failure and cardiac cachexia and the protective role of cardiac obesity. We also set the basis for possible screening methods that may allow for a timely diagnosis of cardiac cachexia, since there is still no cure for this condition. Several therapeutic procedures are discussed including exercise, nutritional proposals, myostatin antibodies, ghrelin, anabolic steroids, anti-inflammatory substances, beta-adrenergic agonists, medroxyprogesterone acetate, megestrol acetate, cannabinoids, statins, thalidomide, proteasome inhibitors and pentoxifylline. However, to this date, there is no cure for cachexia.

PMID:35326490 | PMC:PMC8946995 | DOI:10.3390/cells11061039

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