D'Amato Andrea, Prosperi Silvia, Severino Paolo, Myftari Vincenzo, Correale Michele, Perrone Filardi Pasquale, Badagliacca Roberto, Fedele Francesco, Vizza Carmine Dario, Palazzuoli Alberto
Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, 'Sapienza' University of Rome, Policlinico 'Umberto I' of Rome, 00161 Rome, Italy.
Cardiothoracic Department, 'Policlinico Riuniti' University Hospital, 71100 Foggia, Italy.
J Clin Med. 2024 Dec 12;13(24):7560. doi: 10.3390/jcm13247560.
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. In many maladaptive processes, the role of microRNAs (miRNAs) has been recently demonstrated. MiRNAs are small endogenous non-coding molecules of RNA involved in gene expression regulation, and they play a pivotal role in intercellular communication, being involved in different biological and pathophysiological processes. MiRNAs can modulate infarct area size, cardiomyocytes restoration, collagen deposition, and macrophage polarization. MiRNAs may be considered as specific biomarkers of hypertrophy and fibrosis. MiRNAs have been proposed as a therapeutical tool because their administration can contrast with myocardial pathophysiological remodeling leading to HF. Antimir and miRNA mimics are small oligonucleotides which may be administered in several manners and may be able to regulate the expression of specific and circulating miRNAs. Studies on animal models and on healthy humans demonstrate that these molecules are well tolerated and effective, opening the possibility of a therapeutic use of miRNAs in cases of HF. The application of miRNAs for diagnosis, prognostic stratification, and therapy fits in with the new concept of a personalized and tailored approach to HF.
心力衰竭(HF)具有多方面且复杂的病理生理学机制。除了神经激素、肾素 - 血管紧张素 - 醛固酮系统以及肾上腺素能过度激活外,其他病理生理决定因素的作用也日益显现。遗传和表观遗传因素参与了该综合征。在许多适应性不良过程中,微小RNA(miRNA)的作用最近已得到证实。miRNA是参与基因表达调控的内源性小非编码RNA分子,它们在细胞间通讯中起关键作用,参与不同的生物学和病理生理过程。miRNA可调节梗死面积大小、心肌细胞修复、胶原蛋白沉积和巨噬细胞极化。miRNA可被视为肥大和纤维化的特异性生物标志物。由于miRNA的施用可对抗导致HF的心肌病理生理重塑,因此它们已被提议作为一种治疗工具。抗miRNA和miRNA模拟物是小寡核苷酸,可通过多种方式施用,并可能能够调节特定和循环miRNA的表达。对动物模型和健康人类的研究表明,这些分子耐受性良好且有效,为在HF病例中治疗性使用miRNA开辟了可能性。miRNA在诊断、预后分层和治疗中的应用符合针对HF的个性化和量身定制方法的新概念。