Role of genetic polymorphisms of ion channels in the pathophysiology of coronary microvascular dysfunction and ischemic heart disease.
Role of genetic polymorphisms of ion channels in the pathophysiology of coronary microvascular dysfunction and ischemic heart disease.
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DOI：
10.1007/s00395-013-0387-4
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发表时间：
2013-11
影响因子：
9.5
通讯作者：
Guadagni F
中科院分区：
文献类型：
--
作者：
Fedele F;Mancone M;Chilian WM;Severino P;Canali E;Logan S;De Marchis ML;Volterrani M;Palmirotta R;Guadagni F
传统上，缺血性心脏病（IHD）等同于大血管冠状动脉疾病。然而，最近的证据表明，在缺血性心脏病的病因中，微血管调节受损的作用。由于冠状动脉血流的调节可能涉及特定离子通道的活性，以及内皮依赖性舒张的关键因素，我们提出离子通道或特定内皮调节因子的遗传异常可能是冠状动脉微血管疾病的基础。我们的目的是评估冠状动脉血管中表达的离子通道编码基因的单核苷酸多态性的临床影响，以及与微血管功能障碍导致的IHD的可能相关性。入选了242名连续患者，他们是冠状动脉造影术的候选人。进行了一项前瞻性、观察性、单中心研究，分析了与（1）编码内皮型一氧化氮合酶（eNOS）的NOS 3;（2）编码Ca 2 +/H+-ATP酶泵（SERCA）的ATP 2A 2;（3）编码电压依赖性Na+通道的SCN 5A KCNJ 8和KCNJ 11分别编码K-ATP通道的Kir6.1和Kir6.2亚基;（5）KCN 5A编码电压门控K+通道（Kv1.5）。未观察到临床IHD表现与SERCA、Kir6.1和Kv1.5多态性之间的显著相关性（p > 0.05），而eNOS以及Kir6.2和Nav1.5中检测到的特异性多态性与IHD和微血管功能障碍相关。有趣的是，离子通道的遗传多态性似乎具有重要的临床影响，影响微血管功能障碍和IHD的易感性，独立于经典的心血管危险因素的存在。
Conventionally, ischemic heart disease (IHD) is equated with large vessel coronary disease. However, recent evidence has suggested a role of compromised microvascular regulation in the etiology of IHD. Because regulation of coronary blood flow likely involves activity of specific ion channels, and key factors involved in endothelium-dependent dilation, we proposed that genetic anomalies of ion channels or specific endothelial regulators may underlie coronary microvascular disease. We aimed to evaluate the clinical impact of single-nucleotide polymorphisms in genes encoding for ion channels expressed in the coronary vasculature and the possible correlation with IHD resulting from microvascular dysfunction. 242 consecutive patients who were candidates for coronary angiography were enrolled. A prospective, observational, single-center study was conducted, analyzing genetic polymorphisms relative to (1) NOS3 encoding for endothelial nitric oxide synthase (eNOS); (2) ATP2A2 encoding for the Ca2+/H+-ATPase pump (SERCA); (3) SCN5A encoding for the voltage-dependent Na+ channel (Nav1.5); (4) KCNJ8 and KCNJ11 encoding for the Kir6.1 and Kir6.2 subunits of K-ATP channels, respectively; and (5) KCN5A encoding for the voltage-gated K+ channel (Kv1.5). No significant associations between clinical IHD manifestations and polymorphisms for SERCA, Kir6.1, and Kv1.5 were observed (p > 0.05), whereas specific polymorphisms detected in eNOS, as well as in Kir6.2 and Nav1.5 were found to be correlated with IHD and microvascular dysfunction. Interestingly, genetic polymorphisms for ion channels seem to have an important clinical impact influencing the susceptibility for microvascular dysfunction and IHD, independent of the presence of classic cardiovascular risk factors.
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电压依赖性K+和Ca2+通道对冠状动脉自动调节的贡献。
影响因子：
9.5
作者：
Berwick ZC;Moberly SP;Kohr MC;Morrical EB;Kurian MM;Dick GM;Tune JD
通讯作者：
Tune JD
影响因子：
5
作者：
Glukhov, Alexey V.;Flagg, Thomas P.;Fedorov, Vadim V.;Efimov, Igor R.;Nichols, Colin G.
通讯作者：
Nichols, Colin G.
DOI：
10.1152/ajpheart.01035.2005
发表时间：
2006-12-01
影响因子：
4.8
作者：
Dick, Gregory M.;Katz, Paige S.;Tune, Johnathan D.
通讯作者：
Tune, Johnathan D.
DOI：
10.1152/ajpheart.00637.2007
发表时间：
2007-11-01
影响因子：
4.8
作者：
Fountain, Samuel J.;Cheong, Alex;Beech, David J.
通讯作者：
Beech, David J.
DOI：
10.1152/ajpheart.00057.2003
发表时间：
2003-06-01
影响因子：
4.8
作者：
Gumina, RJ;Pucar, D;Terzic, A
通讯作者：
Terzic, A