Objective: Hypertrophic cardiomyopathy (HCM) is a disease of the myocardium with uncertain etiology and often leads to sudden death as the result of arrhythmia. Pacemaker hyperpolarization-activated current I(f) was altered in hypertrophic hearts and was probably responsible for arrhythmia. I(f) channels are compose\d of four hyperpolarization-activated cyclic nucleotide-gated cation subunits (HCN1-4). A previous study found significantly high levels of HCN2 and HCN4 mRNA in hypertrophic hearts compared to control hearts in septum and left ventricles in rats. No studies, however, have investigated the HCN gene expression in the myocardium from human HCM heart.
Methods: The left ventricular tissue from four patients who died of HCM and six healthy patients who died of motor vehicle accidents was included in this study. The fluorescent quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay was used to detect HCN4 mRNA. The expression of HCN4 mRNA of the two groups was detected on the assay.
Results: In the HCM hearts, disorganization of the hypertrophic myofibers and interstitial fibrosis were observed in all four patients, although absent in healthy control hearts. By quantitative polymerase chain reaction, the mean copy number of HCN4 mRNA was 2.2×10(7) (range, 6.8×10(6) to 4.55×10(7)) in HCM hearts and 8.17×10(3) (range, 8.76×10(1) to 3.5×10(4)) in control hearts (P=.0318).
Conclusion: Higher HCN4 mRNA levels in the HCM hearts suggest that up-regulation of HCN4 gene expression might be responsible for ventricular arrhythmia that leads to sudden death.
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http://dx.doi.org/10.1016/j.carpath.2010.01.007 | DOI Listing |
Front Med (Lausanne)
December 2024
Division of Cardiovascular Sciences, School of Medical Sciences, University of Manchester, Manchester, United Kingdom.
Background: The sinoatrial node (SN) generates the heart rate (HR). Its spontaneous activity is regulated by a complex interplay between the modulation by the autonomic nervous system (ANS) and intrinsic factors including ion channels in SN cells. However, the systemic and intrinsic regulatory mechanisms are still poorly understood.
View Article and Find Full Text PDFCell Biochem Biophys
September 2024
Heart center of the Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China.
Objective: This study aims to investigate the expression profile of miRNAs significantly dysregulated after acute myocardial infarction (AMI) and their potential targets.
Methods: After the establishment of a mouse model of AMI, RNA was extracted from mouse infarcted myocardium. Paired-end sequencing was then performed using the Illumina NovaSeq 6000 system to explore the expression profile of miRNAs.
Thyroid
June 2024
Institute for Experimental Endocrinology, Center of Brain Behavior & Metabolism, University of Lübeck, Lübeck, Germany.
Int Heart J
February 2024
Department of Cardiology, Fourth Affiliated Hospital, Harbin Medical University.
Ivabradine (IVA) reduces heart rate by inhibiting hyperpolarization-activated cyclic nucleotide-gated channels (HCNs), which play a role in the promotion of pacemaker activity in cardiac sinoatrial node cells. HCNs are highly expressed in neural and myocardial tissues and are involved in the modulation of inflammatory neuropathic pain. However, whether IVA exerts any effect on myocardial inflammation in the pathogenesis of heart failure is unclear.
View Article and Find Full Text PDFMol Psychiatry
September 2023
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.
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