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Biomedicine & Pharmacotherapy =... Sep 2023Cardiac hypertrophy is frequently associated with ventricular dysfunction and heart failure. Paeoniflorin, has been widely used to treat cardiovascular...
Cardiac hypertrophy is frequently associated with ventricular dysfunction and heart failure. Paeoniflorin, has been widely used to treat cardiovascular dysfunction-related diseases. However, the underlying mechanism has been unclear. Here, we investigated the potential inhibitory effects and mechanism of paeoniflorin on oxidative stress of cardiac hypertrophy induced by angiotensin II (AngII) in vitro. Using MTS assay, qRT-PCR, WGA staining assay, and western blot, different dosages (50-400 μM) of paeoniflorin were utilized to examine the antihypertrophy effects on H9c2 cells. Western blot examination revealed the presence of apoptosis-related proteins Bax, Bcl2, and Cytc, antioxidative stress-related proteins Nrf2, HO-1, SOD, and CAT, and mitophagy-related proteins PINK1 and Parkin. qRT-PCR was used to detect the mRNA expression of Bax, Bcl2, Nrf2, and HO-1. TUNEL, caspase3/9 enzyme viability, and MDA, T-AOC, and superoxide levels were all evaluated using commercial kits.The fluorescent probes DCFH-DA and JC-1 were employed to measure cellular ROS and MMP levels. Nrf2 siRNA was utilized to investigate Nrf2's role in paeoniflorin-treated cardiac hypertrophy. Paeoniflorin dramatically reduced cell section area (CSA) and hypertrophic marker (ANP, BNP) expression while inhibiting oxidative stress by modulating ROS and MDA, CAT, SOD, and T-AOC levels. Furthermore, in AngII-induced cardiomyocyte hypertrophy, paeoniflorin restores H9c2 apoptosis by restoring Bax, Bcl-2 Cyt-C, Caspase 3, and Caspase 9 levels. Paeoniflorin also restored Nrf2/HO-1 and PINK1/Parkin expression, and its anti-AngII activities were mediated by Nrf2, which was regulated by Nrf2 knockdown. In conclusion, Our data confirm that paeoniflorin alleviates cardiac hypertrophy through modulating oxidative stress and Nrf2 signaling pathway in vitro.
Topics: Animals; Rats; Angiotensin II; Apoptosis; Apoptosis Regulatory Proteins; bcl-2-Associated X Protein; Cardiomegaly; Myocytes, Cardiac; NF-E2-Related Factor 2; Oxidative Stress; Protein Kinases; Proto-Oncogene Proteins c-bcl-2; Rats, Sprague-Dawley; Reactive Oxygen Species; Signal Transduction; Superoxide Dismutase
PubMed: 37542855
DOI: 10.1016/j.biopha.2023.115253 -
Scientific Reports Sep 2023The heart depends on a functional vasculature for oxygenation and transport of nutrients, and it is of interest to learn how primary impairment of the vasculature can...
The heart depends on a functional vasculature for oxygenation and transport of nutrients, and it is of interest to learn how primary impairment of the vasculature can indirectly affect cardiac function and heart morphology. Notch3-deficiency causes vascular smooth muscle cell (VSMC) loss in the vasculature but the consequences for the heart remain largely elusive. Here, we demonstrate that Notch3 mice have enlarged hearts with left ventricular hypertrophy and mild fibrosis. Cardiomyocytes were hypertrophic but not hyperproliferative, and the expression of several cardiomyocyte markers, including Tnt2, Myh6, Myh7 and Actn2, was altered. Furthermore, expression of genes regulating the metabolic status of the heart was affected: both Pdk4 and Cd36 were downregulated, indicating a metabolic switch from fatty acid oxidation to glucose consumption. Notch3 mice furthermore showed lower liver lipid content. Notch3 was expressed in heart VSMC and pericytes but not in cardiomyocytes, suggesting that a perturbation of Notch signalling in VSMC and pericytes indirectly impairs the cardiomyocytes. In keeping with this, Pdgfb mice, characterized by reduced numbers of VSMC and pericytes, showed left ventricular and cardiomyocyte hypertrophy. In conclusion, we demonstrate that reduced Notch3 or PDGFB signalling in vascular mural cells leads to cardiomyocyte dysfunction.
Topics: Animals; Mice; Becaplermin; Cardiomegaly; Hypertrophy, Left Ventricular; Lipid Metabolism; Myocytes, Cardiac; Proto-Oncogene Proteins c-sis
PubMed: 37699967
DOI: 10.1038/s41598-023-42010-7 -
Journal of the American Veterinary... Nov 2023Feline hypertrophic cardiomyopathy (HCM) remains a disease with little therapeutic advancement. Rapamycin modulates the mTOR pathway, preventing and reversing cardiac...
OBJECTIVE
Feline hypertrophic cardiomyopathy (HCM) remains a disease with little therapeutic advancement. Rapamycin modulates the mTOR pathway, preventing and reversing cardiac hypertrophy in rodent disease models. Its use in human renal allograft patients is associated with reduced cardiac wall thickness. We sought to evaluate the effects of once-weekly delayed-release (DR) rapamycin over 6 months on echocardiographic, biochemical, and biomarker responses in cats with subclinical, nonobstructive HCM.
ANIMALS
43 client-owned cats with subclinical HCM.
METHODS
Cats enrolled in this double-blinded, multicentered, randomized, and placebo-controlled clinical trial were allocated to low- or high-dose DR rapamycin or placebo. Cats underwent physical examination, quality-of-life assessment, blood pressure, hematology, biochemistry, total T4, urinalysis, N-terminal pro-B-type natriuretic peptide, and cardiac troponin I at baseline and days 60, 120, and 180. Fructosamine was analyzed at screening and day 180. Echocardiograms were performed at all time points excluding day 120. Outcome variables were compared using a repeated measures ANCOVA.
RESULTS
No demographic, echocardiographic, or clinicopathologic values were significantly different between study groups at baseline, confirming successful randomization. At day 180, the primary study outcome variable, maximum LV myocardial wall thickness at any location, was significantly lower in the low-dose DR rapamycin group compared to placebo (P = .01). Oral DR rapamycin was well tolerated with no significant differences in adverse events between groups.
CLINICAL RELEVANCE
Results demonstrate that DR rapamycin was well tolerated and may prevent or delay progressive LV hypertrophy in cats with subclinical HCM. Additional studies are warranted to confirm and further characterize these results.
Topics: Animals; Cats; Cardiomyopathy, Hypertrophic; Cat Diseases; Heart; Hypertrophy, Left Ventricular; Myocardium; Sirolimus; Delayed-Action Preparations
PubMed: 37495229
DOI: 10.2460/javma.23.04.0187 -
Hypertension Research : Official... May 2024
Topics: Hypertrophy, Left Ventricular; Humans; Hypertension
PubMed: 38467796
DOI: 10.1038/s41440-024-01634-6 -
Journal of the American College of... Aug 2023Ventricular mass responds to changes in physical activity and loading, with cardiac hypertrophy after exercise training, and cardiac atrophy after sustained inactivity....
BACKGROUND
Ventricular mass responds to changes in physical activity and loading, with cardiac hypertrophy after exercise training, and cardiac atrophy after sustained inactivity. Ventricular wall stress (ie, loading) decreases during microgravity. Cardiac atrophy does not plateau during 12 weeks of simulated microgravity but is mitigated by concurrent exercise training.
OBJECTIVES
The goal of this study was to determine whether the current exercise countermeasures on the International Space Station (ISS) offset cardiac atrophy during prolonged space flight.
METHODS
We measured left ventricular (LV) and right ventricular (RV) mass and volumes (via magnetic resonance imaging) in 13 astronauts (4 females; age 49 ± 4 years), between 75 and 60 days before and 3 days after 155 ± 31 days aboard the ISS. Furthermore, we assessed total cardiac work between 21 and 7 days before space flight and 15 days before the end of the mission. Data were compared via paired-samples t-tests.
RESULTS
Total cardiac work was lower during space flight (P = 0.008); however, we observed no meaningful difference in LV mass postflight (pre: 115 ± 30 g vs post: 118 ± 29 g; P = 0.053), with marginally higher LV stroke volume (P = 0.074) and ejection fraction postflight (P = 0.075). RV mass (P = 0.999), RV ejection fraction (P = 0.147), and ventricular end-diastolic (P = 0.934) and end-systolic volumes (P = 0.145) were not different postflight. There were strong positive correlations between the relative change in LV mass with the relative changes in total cardiac output (r = 0.73; P = 0.015) and total cardiac work (r = 0.53; P = 0.112).
CONCLUSIONS
The current exercise countermeasures used on the ISS appear effective in offsetting reductions in cardiac mass and volume, despite overall reductions in total cardiac work, during prolonged space flight.
Topics: Female; Humans; Middle Aged; Heart; Space Flight; Heart Ventricles; Atrophy; Cardiac Output
PubMed: 37587578
DOI: 10.1016/j.jacc.2023.05.058 -
Heart Failure Reviews Mar 2024End-stage renal disease (ESRD) is a common but profound clinical condition, and it is associated with extremely increased morbidity and mortality. ESRD can represent... (Review)
Review
End-stage renal disease (ESRD) is a common but profound clinical condition, and it is associated with extremely increased morbidity and mortality. ESRD can represent four major echocardiographic findings-myocardial hypertrophy, heart failure, valvular calcification, and pericardial effusion. Multiple factors interplay leading to these abnormalities, including pressure/volume overload, oxidative stress, and neurohormonal imbalances. Uremic cardiomyopathy is characterized by left ventricular (LV) hypertrophy and marked diastolic dysfunction. In ESRD patients on hemodialysis, LV geometry is changeable bidirectionally between concentric and eccentric hypertrophy, depending upon changes in corporal fluid volume and arterial pressure, which eventually results in a characteristic of LV systolic dysfunction. Speckle tracking echocardiography enabling to detect subclinical disease might help prevent future advancement to heart failure. Heart valve calcification also is common in ESRD, keeping in mind which progresses faster than expected. In a modern era, pericardial effusion observed in ESRD patients tends to result from volume overload, rather than pericarditis. In this review, we introduce and discuss those four echocardiography-assessed findings of ESRD, with which known and conceivable pathophysiologies for each are incorporated.
Topics: Humans; Pericardial Effusion; Kidney Failure, Chronic; Echocardiography; Renal Dialysis; Hypertrophy, Left Ventricular; Heart Failure; Cardiomyopathies
PubMed: 38071738
DOI: 10.1007/s10741-023-10376-5 -
Biomedicine & Pharmacotherapy =... Dec 2023Heart failure has become a public health problem that we cannot avoid choosing to face in today's context. In the case of heart failure, pathological cardiac hypertrophy... (Review)
Review
Heart failure has become a public health problem that we cannot avoid choosing to face in today's context. In the case of heart failure, pathological cardiac hypertrophy plays a major role because of its condition of absolute increase in ventricular mass under various stresses. Ferroptosis, it could be defined as regulatory mechanisms that regulate cell death in the absence of apoptosis in iron-dependent cells. This paper introduces various new research findings on the use of different regulatory mechanisms of cellular ferroptosis for the treatment of heart failure and cardiac hypertrophy, providing new therapeutic targets and research directions for clinical treatment. The role and mechanism of ferroptosis in the field of heart failure has been increasingly demonstrated, and the relationship between cardiac hypertrophy, which is one of the causes of heart failure, is also an area of research that we should focus on. In addition, the latest applications and progress of inducers and inhibitors of ferroptosis are reported in this paper, updating the breakthroughs in their fields.
Topics: Humans; Ferroptosis; Heart Failure; Apoptosis; Cell Death; Cardiomegaly
PubMed: 37879210
DOI: 10.1016/j.biopha.2023.115765 -
Journal of the American Society of... Jun 2024Hypertrophic cardiomyopathy (HCM), the most common inherited cardiomyopathy, exhibits left ventricular hypertrophy not secondary to other causes, with varied phenotypic... (Review)
Review
Hypertrophic cardiomyopathy (HCM), the most common inherited cardiomyopathy, exhibits left ventricular hypertrophy not secondary to other causes, with varied phenotypic expression. Enhanced actin-myosin interaction underlies excessive myocardial contraction, frequently resulting in dynamic obstruction within the left ventricle. Left ventricular outflow tract obstruction, occurring at rest or with provocation in 75% of HCM patients, portends adverse prognosis, contributes to symptoms, and is frequently a therapeutic target. Transthoracic echocardiography plays a crucial role in the screening, initial diagnosis, management, and risk stratification of HCM. Herein, we explore echocardiographic evaluation of HCM, emphasizing Doppler assessment for obstruction. Echocardiography informs management strategies through noninvasive hemodynamic assessment, which is frequently obtained with various provocative maneuvers. Recognition of obstructive HCM phenotypes and associated anatomical abnormalities guides therapeutic decision-making. Doppler echocardiography allows monitoring of therapeutic responses, whether it be medical therapies (including cardiac myosin inhibitor therapy) or septal reduction therapies, including surgical myectomy and alcohol septal ablation. This article discusses the hemodynamics of obstruction and practical application of Doppler assessment in HCM. In addition, it provides a visual atlas of obstruction in HCM, including high-quality figures and complementary videos that illustrate the many facets of dynamic obstruction.
Topics: Humans; Cardiomyopathy, Hypertrophic; Ventricular Outflow Obstruction; Echocardiography, Doppler; Echocardiography; Heart Ventricles
PubMed: 38428652
DOI: 10.1016/j.echo.2024.02.010 -
Circulation Sep 2023In hypertrophic cardiomyopathy (HCM), myocyte disarray and microvascular disease (MVD) have been implicated in adverse events, and recent evidence suggests that these...
BACKGROUND
In hypertrophic cardiomyopathy (HCM), myocyte disarray and microvascular disease (MVD) have been implicated in adverse events, and recent evidence suggests that these may occur early. As novel therapy provides promise for disease modification, detection of phenotype development is an emerging priority. To evaluate their utility as early and disease-specific biomarkers, we measured myocardial microstructure and MVD in 3 HCM groups-overt, either genotype-positive (G+LVH+) or genotype-negative (G-LVH+), and subclinical (G+LVH-) HCM-exploring relationships with electrical changes and genetic substrate.
METHODS
This was a multicenter collaboration to study 206 subjects: 101 patients with overt HCM (51 G+LVH+ and 50 G-LVH+), 77 patients with G+LVH-, and 28 matched healthy volunteers. All underwent 12-lead ECG, quantitative perfusion cardiac magnetic resonance imaging (measuring myocardial blood flow, myocardial perfusion reserve, and perfusion defects), and cardiac diffusion tensor imaging measuring fractional anisotropy (lower values expected with more disarray), mean diffusivity (reflecting myocyte packing/interstitial expansion), and second eigenvector angle (measuring sheetlet orientation).
RESULTS
Compared with healthy volunteers, patients with overt HCM had evidence of altered microstructure (lower fractional anisotropy, higher mean diffusivity, and higher second eigenvector angle; all <0.001) and MVD (lower stress myocardial blood flow and myocardial perfusion reserve; both <0.001). Patients with G-LVH+ were similar to those with G+LVH+ but had elevated second eigenvector angle (<0.001 after adjustment for left ventricular hypertrophy and fibrosis). In overt disease, perfusion defects were found in all G+ but not all G- patients (100% [51/51] versus 82% [41/50]; =0.001). Patients with G+LVH- compared with healthy volunteers similarly had altered microstructure, although to a lesser extent (all diffusion tensor imaging parameters; <0.001), and MVD (reduced stress myocardial blood flow [=0.015] with perfusion defects in 28% versus 0 healthy volunteers [=0.002]). Disarray and MVD were independently associated with pathological electrocardiographic abnormalities in both overt and subclinical disease after adjustment for fibrosis and left ventricular hypertrophy (overt: fractional anisotropy: odds ratio for an abnormal ECG, 3.3, =0.01; stress myocardial blood flow: odds ratio, 2.8, =0.015; subclinical: fractional anisotropy odds ratio, 4.0, =0.001; myocardial perfusion reserve odds ratio, 2.2, =0.049).
CONCLUSIONS
Microstructural alteration and MVD occur in overt HCM and are different in G+ and G- patients. Both also occur in the absence of hypertrophy in sarcomeric mutation carriers, in whom changes are associated with electrocardiographic abnormalities. Measurable changes in myocardial microstructure and microvascular function are early-phenotype biomarkers in the emerging era of disease-modifying therapy.
Topics: Humans; Hypertrophy, Left Ventricular; Sarcomeres; Diffusion Tensor Imaging; Genetic Predisposition to Disease; Mutation; Cardiomyopathy, Hypertrophic; Phenotype; Biomarkers; Fibrosis
PubMed: 37463608
DOI: 10.1161/CIRCULATIONAHA.123.063835 -
The Annals of Thoracic Surgery Feb 2024More than half of symptomatic patients with hypertrophic cardiomyopathy (HCM) have left ventricular outflow tract (LVOT) obstruction. Septal reduction therapy by septal... (Review)
Review
More than half of symptomatic patients with hypertrophic cardiomyopathy (HCM) have left ventricular outflow tract (LVOT) obstruction. Septal reduction therapy by septal myectomy can dramatically relieve exertional dyspnea, chest pain, and presyncope in properly selected patients and is an important management pathway for many patients. The distribution and degree of hypertrophy in patients with obstructive HCM are variable and, as discussed in this review, can influence clinical manifestations of the disease and surgical management. Subaortic septal hypertrophy is the most common phenotype of obstructive HCM associated with LVOT obstruction, but midventricular obstruction and apical hypertrophy may occur in isolation or in conjunction with subaortic septal hypertrophy. In many comprehensive HCM centers, transaortic septal myectomy is the preferred method of septal reduction therapy for symptomatic patients with obstructive HCM. Early surgical approaches aimed at alleviating left LVOT obstruction were hampered by a lack of understanding of the anatomy and pathophysiology of obstructive HCM. With the advent of Doppler echocardiography and, more recently, cardiac magnetic resonance imaging, surgeons can precisely assess the location and degree of obstruction, left ventricular size and function, and morphology and function of the mitral valve. This review discusses the current understanding of the role of septal myectomy in the management of patients with HCM and details contemporary operative methods.
Topics: Humans; Cardiac Surgical Procedures; Ventricular Outflow Obstruction, Left; Cardiomyopathy, Hypertrophic; Mitral Valve; Hypertrophy; Ventricular Outflow Obstruction; Treatment Outcome
PubMed: 37914148
DOI: 10.1016/j.athoracsur.2023.10.026