scholarly journals Role of genetic polymorphisms of ion channels in the pathophysiology of coronary microvascular dysfunction and ischemic heart disease

2013 ◽  
Vol 108 (6) ◽  
Author(s):  
Francesco Fedele ◽  
Massimo Mancone ◽  
William M. Chilian ◽  
Paolo Severino ◽  
Emanuele Canali ◽  
...  
Keyword(s):  
Heart Disease ◽  
Ion Channels ◽  
Ischemic Heart Disease ◽  
Genetic Polymorphisms ◽  
Microvascular Dysfunction ◽  
Ischemic Heart ◽  
Coronary Microvascular Dysfunction

scholarly journals Ischemic Heart Disease and Heart Failure: Role of Coronary Ion Channels

2020 ◽  
Vol 21 (9) ◽  
pp. 3167 ◽  
Author(s):  
Paolo Severino ◽  
Andrea D’Amato ◽  
Mariateresa Pucci ◽  
Fabio Infusino ◽  
Lucia Ilaria Birtolo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Flow ◽  
Heart Disease ◽  
Ion Channels ◽  
Myocardial Ischemia ◽  
Ischemic Heart Disease ◽  
Microvascular Dysfunction ◽  
Ischemic Heart ◽  
Coronary Microvascular Dysfunction

Heart failure is a complex syndrome responsible for high rates of death and hospitalization. Ischemic heart disease is one of the most frequent causes of heart failure and it is normally attributed to coronary artery disease, defined by the presence of one or more obstructive plaques, which determine a reduced coronary blood flow, causing myocardial ischemia and consequent heart failure. However, coronary obstruction is only an element of a complex pathophysiological process that leads to myocardial ischemia. In the literature, attention paid to the role of microcirculation, in the pathophysiology of ischemic heart disease and heart failure, is growing. Coronary microvascular dysfunction determines an inability of coronary circulation to satisfy myocardial metabolic demands, due to the imbalance of coronary blood flow regulatory mechanisms, including ion channels, leading to the development of hypoxia, fibrosis and tissue death, which may determine a loss of myocardial function, even beyond the presence of atherosclerotic epicardial plaques. For this reason, ion channels may represent the link among coronary microvascular dysfunction, ischemic heart disease and consequent heart failure.

Abstract 19305: Diabetes Mellitus and Ischemic Heart Disease Susceptibility: Which is the Influence of Genetic Polymorphisms for Katp Channels?

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Paolo Severino ◽  
Alessandra Cinque ◽  
Nicolò Salvi ◽  
Giorgio Calabrese ◽  
Alessandra Armato ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Disease ◽  
Ion Channels ◽  
Ischemic Heart Disease ◽  
Genetic Polymorphisms ◽  
Coronary Arteries ◽  
Microvascular Dysfunction ◽  
Katp Channels ◽  
Diabetic Patients ◽  
Normal Coronary Arteries

Background: Evidences show that diabetes mellitus (DM) lead to higher risk for ischemic heart disease (IHD). Recently, we proposed that genetic polymorphisms (SNP) of coronary ion channels might be involved in IHD. We showed that the genotype distribution of SNP rs5215 for Kir6.2 subunit of ATP-dependent potassium (KATP) channels moderately deviated from the HW equilibrium and that rs5215_GG is linked to IHD susceptibility: it might have a ‘‘protective’’ role in IHD genesis. Moreover, previous studies described that SNP rs5215_GG is strongly correlated with DM and hyperinsulinism in human. Aim and methods: In the present study, we hypothesized that SNP rs5215_GG for Kir6.2 subunit for KATP channels had some influences in the susceptibility of DM to IHD. We performed a subgroup analysis about the influence of rs5215_GG in diabetic patients on our previous population, i.e. 242 patients candidates to elective or emergency coronary angiography for acute coronary syndrome or chronic angina, of which 155 with CAD, 46 with microvascular dysfunction and 41 with anatomically and functionally normal coronary arteries (control group). Results: Among 242 patients, comparing subjects with DM to those without, there was not any significant difference in the prevalence of rs5215_GG. However, among 33 subjects without DM with normal coronary arteries, SNP rs5215_GG had a higher prevalence compared to those in the CAD group (10/33; 30.3%; p= 0.0277) as well as non-diabetic patients in the microvascular dysfunction group (9/33; 27.2%; p= 0.0295). Discussion and conclusion: The variant rs5215_GG results in the substitution of isoleucine (I) residue with valine (V) in the Kir6.2 subunit of KATP channels. Our results confirm that rs5215_GG might decrease susceptibility to IHD in patients without DM. In fact, rs5215_GG was confirmed to be present more frequently in patients without DM presenting anatomically and functionally normal coronary arteries. We believe that absence of DM is protective against IHD genesis and it might be improved by coronary KATP channels expressing rs5215_GG. Taken together, our data ratify the possibility that ion channels play a key role in coronary homeostasis and that SNP encoding for ion channels are involved in IHD pathophysiology.

scholarly journals Diabetes Mellitus and Ischemic Heart Disease: The Role of Ion Channels

2018 ◽  
Vol 19 (3) ◽  
pp. 802 ◽  
Author(s):  
Paolo Severino ◽  
Andrea D’Amato ◽  
Lucrezia Netti ◽  
Mariateresa Pucci ◽  
Marialaura De Marchis ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Disease ◽  
Ion Channels ◽  
Ischemic Heart Disease ◽  
Ischemic Heart

Abstract 18437: Women and Ischemic Heart Disease: Which Role for Katp Channels?

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Paolo Severino ◽  
Simone Calcagno ◽  
Mariateresa Pucci ◽  
Maria Laura De Marchis ◽  
Raffaele Palmirotta ◽  
...  
Keyword(s):  
Heart Disease ◽  
Ion Channels ◽  
Ischemic Heart Disease ◽  
Coronary Arteries ◽  
Protective Factor ◽  
Microvascular Dysfunction ◽  
Katp Channels ◽  
Protective Role ◽  
Ischemic Heart ◽  
Normal Coronary Arteries

Background: In the last decades, scientists have been studying the pathophysiology of ischemic heart disease (IHD) in women. In fact, as it is well known, in women IHD differs in term of pathogenesis, symptoms and prognosis. Different risk factors and mechanisms of disease may be at work in women. Genetic polymorphisms (SNP) for coronary ion channels may be involved in IHD susceptibility. In particular, the SNP rs5215 for Kir6.2 subunit of ATP-dependent potassium (KATP) channels has been proposed as a protective factor in IHD susceptibility, mostly in women. Aim and methods: To confirm the preliminary encouraging results on the protective role SNP rs5215_GG in IHD susceptibility for women, we enrolled 460 consecutive patients (144 women) with an indication to undergo coronary angiography for suspected ischemic heart disease, performing intracoronary functional tests in patients showing anatomically normal arteries to evaluate coronary microvascular function. We analyzed SNPs relative to the Kir6.2 subunit of KATP channels. Results: Among 460 patients, 330 presented with CAD (72 women), 68 with microvascular dysfunction (39 women) and 62 with anatomically and functionally normal coronary arteries (33 women). The SNP rs5215_GG was found to be more frequent in women compared to men (21/144 -14.6%, vs. 36/316 -11.3%; p=0.36). In particular, rs5215_GG was more frequent in ladies with anatomically and functionally normal coronary arteries compared with women presenting CAD (9/33 -27.2% vs. 7/72 -9.7%; p=0.037), whereas there was no difference between men in normal and CAD groups. Discussion and conclusion: Our data validate the hypothesis that rs5215_GG could reduce susceptibility to IHD in women, since it is more frequent in ladies presenting anatomically and functionally normal coronary arteries. The results suggest that KATP channels with rs5215_GG could be protective against IHD. Our data endorse the prospect of associations between SNP encoding coronary ion channels and IHD, validating the idea that ion channels play in coronary homeostasis and that their polymorphisms act in IHD genesis.

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