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Biomedicine & Pharmacotherapy =... Jan 2024The heart undergoes pathological cardiac hypertrophy as an adaptive response to prolonged pathological stimulation, leading to cardiomyocyte hypertrophy, fibroblast...
The heart undergoes pathological cardiac hypertrophy as an adaptive response to prolonged pathological stimulation, leading to cardiomyocyte hypertrophy, fibroblast proliferation, and an increase in extracellular matrix. Chinese medicine monomers are now receiving much attention for the treatment of cardiac hypertrophy and myocardial remodeling. Biochanin A (BCA) is a kind of flavonoid structural monomer, which has a certain therapeutic effect on bone thinning disease, aging syndrome, lung cancer, etc. Moreover, it exhibits hypoglycemic, anti-inflammatory, anti-oxidation, anti-bacteria and other pharmacological properties. It is still unknown whether BCA has an impact on the mechanism of TAC-induced cardiac hypertrophy. Here, cardiac remodeling was induced by TAC. BCA was injected intraperitoneally at 25 and 50 mg/kg/day one week in advance. Masson, WGA, DHE and other pathological staining and serum were used to detect the inhibitory effect of BCA on cardiac hypertrophy in mice. The anti-hypertrophic effect of BCA was demonstrated by studying the pathological manifestations of Neonatal rat cardiomyocytes (NRCMs) and cardiac fibroblasts (CFs) in vitro. The results showed that BCA significantly reduced TAC-induced fibrosis, inflammation, oxidative stress, and myocardial hypertrophy. BCA inhibited Ang II-induced cell hypertrophy and oxidative stress in NRCMs in vitro and Ang II-induced CF migration, proliferation, and collagen secretion. This suggests that BCA plays a key role in inhibiting the progression of myocardial remodeling, suggesting that BCA may be a promising agent for the treatment of myocardial hypertrophy and fibrosis.
Topics: Rats; Mice; Animals; Cardiomegaly; Myocardium; Myocytes, Cardiac; Fibrosis; Mice, Inbred C57BL; Angiotensin II; Ventricular Remodeling
PubMed: 38091641
DOI: 10.1016/j.biopha.2023.116002 -
Frontiers in Nephrology 2023Dialysis patients experience 10-20 times higher cardiovascular mortality than the general population. The high burden of both conventional and nontraditional risk... (Review)
Review
Dialysis patients experience 10-20 times higher cardiovascular mortality than the general population. The high burden of both conventional and nontraditional risk factors attributable to loss of renal function can explain higher rates of cardiovascular disease (CVD) morbidity and death among dialysis patients. As renal function declines, uremic toxins accumulate in the blood and disrupt cell function, causing cardiovascular damage. Hemodialysis patients have many cardiovascular complications, including sudden cardiac death. Peritoneal dialysis puts dialysis patients with end-stage renal disease at increased risk of CVD complications and emergency hospitalization. The current standard of care in this population is based on observational data, which has a high potential for bias due to the paucity of dedicated randomized clinical trials. Furthermore, guidelines lack specific guidelines for these patients, often inferring them from non-dialysis patient trials. A crucial step in the prevention and treatment of CVD would be to gain better knowledge of the influence of these predisposing risk factors. This review highlights the current evidence regarding the influence of advanced chronic disease on the cardiovascular system in patients undergoing renal dialysis.
PubMed: 37840653
DOI: 10.3389/fneph.2023.1198560 -
The American Journal of Cardiology Feb 2024Hypertrophic cardiomyopathy (HCM) is a complex, heterogeneous disorder that affects approximately 1 in every 500 persons worldwide and about 750,000 Americans. It is... (Review)
Review
Hypertrophic cardiomyopathy (HCM) is a complex, heterogeneous disorder that affects approximately 1 in every 500 persons worldwide and about 750,000 Americans. It is characterized by left ventricular hypertrophy that is usually asymmetric, with enlarged myocytes in disarray, unexplained by loading conditions. Obstruction to left ventricular outflow occurs in approximately 60% of patients. The natural history and cardiac morphology of HCM are quite heterogeneous. Although most patients with HCM are asymptomatic or mildly symptomatic, a minority are disabled by dyspnea, angina, or syncope, develop advanced heart failure, or die suddenly.
Topics: Humans; Cardiomyopathy, Hypertrophic; Death, Sudden, Cardiac; Heart Failure; Heart Ventricles; Hypertrophy, Left Ventricular; Syncope
PubMed: 38368032
DOI: 10.1016/j.amjcard.2023.10.075 -
Cells Jul 2023Heart failure and cancer are the deadliest diseases worldwide. Murine models for cardiac remodeling and heart failure demonstrate that cardiac dysfunction promotes...
Heart failure and cancer are the deadliest diseases worldwide. Murine models for cardiac remodeling and heart failure demonstrate that cardiac dysfunction promotes cancer progression and metastasis spread. Yet, no information is available on whether and how tumor progression affects cardiac remodeling. Here, we examined cardiac remodeling following transverse aortic constriction (TAC) in the presence or absence of proliferating cancer cells. We show that tumor-bearing mice, of two different cancer cell lines, display reduced cardiac hypertrophy, lower fibrosis and improved cardiac contractile function following pressure overload induced by TAC surgery. Integrative analysis of qRT-PCR, flow cytometry and immunofluorescence identified tumor-dependent M1-to-M2 polarization in the cardiac macrophage population as a mediator of the beneficial tumor effect on the heart. Importantly, tumor-bearing mice lacking functional macrophages fail to improve cardiac function and display sustained fibrosis.
Topics: Mice; Animals; Ventricular Remodeling; Heart Failure; Heart; Neoplasms; Fibrosis
PubMed: 37508517
DOI: 10.3390/cells12141853 -
JACC. Basic To Translational Science Sep 2023
PubMed: 37791303
DOI: 10.1016/j.jacbts.2023.06.002 -
Journal of the American Heart... Feb 2024Alveolar hypoxia is protective in the context of cardiovascular and ischemic heart disease; however, the underlying mechanisms are incompletely understood. The present...
BACKGROUND
Alveolar hypoxia is protective in the context of cardiovascular and ischemic heart disease; however, the underlying mechanisms are incompletely understood. The present study sought to test the hypothesis that hypoxia is cardioprotective in left ventricular pressure overload (LVPO)-induced heart failure. We furthermore aimed to test that overlapping mechanisms promote cardiac recovery in heart failure patients following left ventricular assist device-mediated mechanical unloading and circulatory support.
METHODS AND RESULTS
We established a novel murine model of combined chronic alveolar hypoxia and LVPO following transverse aortic constriction (HxTAC). The HxTAC model is resistant to cardiac hypertrophy and the development of heart failure. The cardioprotective mechanisms identified in our HxTAC model include increased activation of HIF (hypoxia-inducible factor)-1α-mediated angiogenesis, attenuated induction of genes associated with pathological remodeling, and preserved metabolic gene expression as identified by RNA sequencing. Furthermore, LVPO decreased and increased mRNA expression under normoxic conditions, which was attenuated under hypoxic conditions and may induce additional hypoxia-mediated cardioprotective effects. Analysis of samples from patients with advanced heart failure that demonstrated left ventricular assist device-mediated myocardial recovery revealed a similar expression pattern for and as observed in HxTAC hearts.
CONCLUSIONS
Hypoxia attenuates LVPO-induced heart failure. Cardioprotective pathways identified in the HxTAC model might also contribute to cardiac recovery following left ventricular assist device support. These data highlight the potential of our novel HxTAC model to identify hypoxia-mediated cardioprotective mechanisms and therapeutic targets that attenuate LVPO-induced heart failure and mediate cardiac recovery following mechanical circulatory support.
Topics: Humans; Mice; Animals; Heart Failure; Cardiomegaly; Myocardium; Aortic Valve Stenosis; Hypoxia; Ventricular Remodeling; Disease Models, Animal
PubMed: 38293923
DOI: 10.1161/JAHA.123.033553 -
Current Hypertension Reports Sep 2023The goal is to review masked hypertension (MH) as a relatively new phenomenon when patients have normal office BP but elevated out-of-office BP. Firstly, it was... (Review)
Review
PURPOSE OF REVIEW
The goal is to review masked hypertension (MH) as a relatively new phenomenon when patients have normal office BP but elevated out-of-office BP. Firstly, it was described in children in 2004. It has received increased attention in the past decade.
RECENT FINDINGS
The prevalence of MH in different pediatric populations differs widely between 0 and 60% based on the population studied, definition of MH, or method of out-of-office BP measurement. The highest prevalence of MH has been demonstrated in children with chronic kidney disease (CKD), obesity, diabetes, and after heart transplantation. In healthy children but with risk factors for hypertension such as prematurity, overweight/obesity, diabetes, chronic kidney disease, or positive family history of hypertension, the prevalence of MH is 9%. In healthy children without risk factors for hypertension, the prevalence of MH is very low ranging 0-3%. In healthy children, only patients with the following clinical conditions should be screened for MH: high-normal/elevated office BP, positive family history of hypertension, and those referred for suspected hypertension who have normal office BP in the secondary/tertiary center.
Topics: Humans; Adolescent; Child; Masked Hypertension; Hypertension; Risk Factors; Obesity; Renal Insufficiency, Chronic
PubMed: 37639176
DOI: 10.1007/s11906-023-01260-6 -
Transplantation Direct Jun 2024Left ventricular hypertrophy (LVH) in patients with end stage renal disease undergoing renal replacement is linked to an increased risk for cardiovascular diseases....
BACKGROUND
Left ventricular hypertrophy (LVH) in patients with end stage renal disease undergoing renal replacement is linked to an increased risk for cardiovascular diseases. Dialysis does not completely prevent or correct this abnormality, and the evidence for kidney transplantation (KT) varies. This analysis aims to explore the relationship between KT and LVH.
METHODS
MEDLINE and Scopus were systematically searched in October 2023. All cross-sectional and longitudinal studies that fulfilled our inclusion criteria were included. Outcome was left ventricular mass index (LVMI) changes. We conducted a meta-analysis using a random effects model. Meta-regression was applied to examine the LVMI changes dependent on various covariates. Sensitivity analysis was used to handle outlying or influential studies and address publication bias.
RESULTS
From 7416 records, 46 studies met the inclusion criteria with 4122 included participants in total. Longitudinal studies demonstrated an improvement of LVMI after KT -0.44 g/m (-0.60 to -0.28). Blood pressure was identified as a predictor of LVMI change. A younger age at the time of KT and well-controlled anemia were also associated with regression of LVH. In studies longitudinally comparing patients on dialysis and renal transplant recipients, no difference was detected -0.09 g/m (-0.33 to 0.16). Meta-regression using changes of systolic blood pressure as a covariate showed an association between higher blood pressure and an increase in LVMI, regardless of the modality of renal replacement treatment.
CONCLUSIONS
In conclusion, our results indicated a potential cardiovascular benefit, defined as the regression of LVH, after KT. This benefit was primarily attributed to improved blood pressure control rather than the transplantation itself.
PubMed: 38769973
DOI: 10.1097/TXD.0000000000001647 -
Heart (British Cardiac Society) Jul 2023Hypertrophic cardiomyopathy (HCM) is characterised by left ventricular hypertrophy (LVH), myocardial fibrosis, enhanced oxidative stress and energy depletion.... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
Hypertrophic cardiomyopathy (HCM) is characterised by left ventricular hypertrophy (LVH), myocardial fibrosis, enhanced oxidative stress and energy depletion. Unbound/loosely bound tissue copper II ions are powerful catalysts of oxidative stress and inhibitors of antioxidants. Trientine is a highly selective copper II chelator. In preclinical and clinical studies in diabetes, trientine is associated with reduced LVH and fibrosis, and improved mitochondrial function and energy metabolism. Trientine was associated with improvements in cardiac structure and function in an open-label study in patients with HCM.
METHODS
The Efficacy and Mechanism of Trientine in Patients with Hypertrophic Cardiomyopathy (TEMPEST) trial is a multicentre, double-blind, parallel group, 1:1 randomised, placebo-controlled phase II trial designed to evaluate the efficacy and mechanism of action of trientine in patients with HCM. Patients with a diagnosis of HCM according to the European Society of Cardiology Guidelines and in New York Heart Association classes I-III are randomised to trientine or matching placebo for 52 weeks. Primary outcome is change in left ventricular (LV) mass indexed to body surface area, measured using cardiovascular magnetic resonance. Secondary efficacy objectives will determine whether trientine improves exercise capacity, reduces arrhythmia burden, reduces cardiomyocyte injury, improves LV and atrial function, and reduces LV outflow tract gradient. Mechanistic objectives will determine whether the effects are mediated by cellular or extracellular mass regression and improved myocardial energetics.
CONCLUSION
TEMPEST will determine the efficacy and mechanism of action of trientine in patients with HCM.
TRIAL REGISTRATION NUMBERS
NCT04706429 and ISRCTN57145331.
Topics: Humans; Trientine; Copper; Cardiomyopathy, Hypertrophic; Heart; Hypertrophy, Left Ventricular; Fibrosis
PubMed: 37137675
DOI: 10.1136/heartjnl-2022-322271