Myocardial Ischemia in Women When Genetic Susceptibility Matters

P. Severino, A. D’Amato, Mariateresa Pucci, M. Mariani, L. Netti, F. Infusino, M. Mancone, F. Fedele
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引用次数: 3

Abstract

Ischemic heart disease is the most common cause of death in both female and male genders. Though coronary artery disease is the most common determinant of ischemia in males, women present more often chest pain associated with normal epicardial coronary arteries. In females, coronary microvascular dysfunction plays a key role in developing symptoms and imbalance between delivery and request of coronary blood flow. Coronary ion channels play a major role in the regulation of coronary blood flow. According to the epidemiological, pathophysiological and clinical differences between male and female genders in ischemic heart diseases, it is legitimate to suspect the possible impact of gender on modulating the effect of cardiovascular risk factors. Whereas it is well known the role of estrogens in cardiovascular system, the role of genetics it has never been extensively addressed. Considering the high prevalence of coronary microvascular dysfunction in females and the regulatory function of coronary ion channels, we speculate that genetic differences in genes encoding the ion channels could be a major determinant of the difference in ischemic phenotypic expression among genders. Our previous study clearly shows that the single nucleotide polymorphism rs5215_GG of KCNJ11 gene encoding for coronary KATP channel is more prevalent in women and reduces the susceptibility to ischemic heart disease regardless the presence of other cardiovascular risk factors. This finding suggests a major role of genetics in the development of ischemic heart diseases and warrants further studies to evaluate the usefulness of genetic screening in clinical daily practice.
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遗传易感性影响女性心肌缺血
缺血性心脏病是女性和男性最常见的死亡原因。尽管冠状动脉疾病是男性缺血最常见的决定因素,但女性更常出现与正常心外膜冠状动脉相关的胸痛。在女性中,冠状动脉微血管功能障碍在出现症状和冠状动脉血流输送和需求之间的不平衡中起关键作用。冠状动脉离子通道在冠状动脉血流调节中起重要作用。根据缺血性心脏病男性和女性的流行病学、病理生理和临床差异,我们有理由怀疑性别可能影响心血管危险因素的调节作用。虽然雌激素在心血管系统中的作用众所周知,但遗传学的作用从未得到广泛的研究。考虑到女性冠状动脉微血管功能障碍的高发率和冠状动脉离子通道的调节功能,我们推测编码离子通道基因的遗传差异可能是性别间缺血性表型表达差异的主要决定因素。我们之前的研究清楚地表明,编码冠状动脉KATP通道的KCNJ11基因的单核苷酸多态性rs5215_GG在女性中更为普遍,并且无论是否存在其他心血管危险因素,都可以降低缺血性心脏病的易感性。这一发现表明遗传学在缺血性心脏病的发展中起着重要作用,值得进一步研究以评估遗传筛查在临床日常实践中的有用性。
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