Cardiac hypertrophy has been demonstrated in rat models of hyperhomocysteinemia, a major risk factor for chronic heart failure. As one of the molecular pathway which leads to cardiac hypertrophy is mediated by the serine-threonine kinase DYRK1A, we have determined the expression of Dyrk1a in the heart of hyperhomocysteinemic rats and found that hyperhomocysteinemia in rats not only induced ventricular cardiomyocyte hypertrophy but also decreased protein Dyrk1a expression. The decreased expression of Dyrk1a could be consistent with decreased antihypertrophic effects of Dyrk1a leading to cardiomyocyte hypertrophy in case of hyperhomocysteinemia.
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http://dx.doi.org/10.1016/j.ijcard.2009.10.043 | DOI Listing |
J Clin Med
December 2024
Cardio Thoracic and Vascular Department, 'S. Maria alle Scotte Hospital', University of Siena, 53100 Siena, Italy.
Heart failure (HF) has a multifaceted and complex pathophysiology. Beyond neurohormonal, renin-angiotensin-aldosterone system, and adrenergic hyperactivation, a role for other pathophysiological determinants is emerging. Genetic and epigenetic factors are involved in this syndrome.
View Article and Find Full Text PDFCells
December 2024
Cardiac Signaling Center, University of South Carolina, Medical University of South Carolina and Clemson University, Charleston, SC 29425, USA.
Over 200 point mutations in the ryanodine receptor (RyR2) of the cardiac sarcoplasmic reticulum (SR) are known to be associated with cardiac arrhythmia. We have already reported on the calcium signaling phenotype of a point mutation in RyR2 Ca binding site Q3925E expressed in human stem-cell-derived cardiomyocytes (hiPSC-CMs) that was found to be lethal in a 9-year-old girl. CRISPR/Cas9-gene-edited mutant cardiomyocytes carrying the RyR2-Q3925E mutation exhibited a loss of calcium-induced calcium release (CICR) and caffeine-triggered calcium release but continued to beat arrhythmically without generating significant SR Ca release, consistent with a remodeling of the calcium signaling pathway.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
January 2025
Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, United States.
Diabetic cardiomyopathy (DMCM), defined as left ventricular dysfunction in the setting of diabetes mellitus without hypertension, coronary artery disease or valvular heart disease, is a well-recognized entity whose prevalence is certainly predicted to increase alongside the rising incidence and prevalence of diabetes mellitus. The pathophysiology of DMCM stems from hyperglycemia and insulin resistance, resulting in oxidative stress, inflammation, cardiomyocyte death, and fibrosis. These perturbations lead to left ventricular hypertrophy with associated impaired relaxation early in the course of the disease, and eventually culminating in combined systolic and diastolic heart failure.
View Article and Find Full Text PDFZhonghua Bing Li Xue Za Zhi
January 2025
Department of Pathology, the Seventh Medical Center of People's Liberation Army of China General Hospital, Beijing100700, China.
To analyze the morphologic changes and the extent of severity in end-stage heart disease; and to explore the correlation with their clinical features. Twelve cases of recipients who underwent pediatric cardiac allograft transplantation were collected from May 2022 to November 2023 at the Seventh Medical Center of People's Liberation Army of China General Hospital. Gross pathologic examinations were performed and morphological changes were observed under a light microscope after HE, Masson's trichrome, and reticulin staining.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Basis Dis
January 2025
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Cardiology, Wuhan 430060, China. Electronic address:
Background: Cardiac hypertrophy is characterized by the upregulation of fetal genes, increased protein synthesis, and enlargement of cardiac myocytes. The mechanistic target of rapamycin complex 1 (mTORC1), which responds to fluctuations in cellular nutrient and energy levels, plays a pivotal role in regulating protein synthesis and cellular growth. While attempts to inhibit mTORC1 activity, such as through the application of rapamycin and its analogs, have demonstrated limited efficacy, further investigation is warranted.
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