Protection against Ischemic Heart Disease: A Joint Role for eNOS and the K<sub>ATP</sub> Channel

Paolo Severino; Andrea D’Amato; Massimo Mancone; Alberto Palazzuoli; Marco Valerio Mariani; Silvia Prosperi; Vincenzo Myftari; Carlo Lavalle; Giovanni Battista Forleo; Lucia Ilaria Birtolo; Viviana Caputo; Fabio Miraldi; Cristina Chimenti; Roberto Badagliacca; Viviana Maestrini; Raffaele Palmirotta; Carmine Dario Vizza; Francesco Fedele

doi:10.3390/ijms24097927

International Journal of Molecular Sciences (Apr 2023)

Protection against Ischemic Heart Disease: A Joint Role for eNOS and the K<sub>ATP</sub> Channel

Paolo Severino,
Andrea D’Amato,
Massimo Mancone,
Alberto Palazzuoli,
Marco Valerio Mariani,
Silvia Prosperi,
Vincenzo Myftari,
Carlo Lavalle,
Giovanni Battista Forleo,
Lucia Ilaria Birtolo,
Viviana Caputo,
Fabio Miraldi,
Cristina Chimenti,
Roberto Badagliacca,
Viviana Maestrini,
Raffaele Palmirotta,
Carmine Dario Vizza,
Francesco Fedele

Affiliations

Paolo Severino: Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Andrea D’Amato: Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Massimo Mancone: Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Alberto Palazzuoli: Cardiovascular Diseases Unit, Cardio Thoracic and Vascular Department, Le Scotte Hospital, University of Siena, 53100 Siena, Italy
Marco Valerio Mariani: Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Silvia Prosperi: Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Vincenzo Myftari: Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Carlo Lavalle: Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Giovanni Battista Forleo: Department of Cardiology, Luigi Sacco University Hospital, 20157 Milan, Italy
Lucia Ilaria Birtolo: Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Viviana Caputo: Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy
Fabio Miraldi: Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Cristina Chimenti: Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Roberto Badagliacca: Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Viviana Maestrini: Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Raffaele Palmirotta: Interdisciplinary Department of Medicine, University of Bari ‘Aldo Moro’, 70121 Bari, Italy
Carmine Dario Vizza: Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Francesco Fedele: Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy

DOI: https://doi.org/10.3390/ijms24097927
Journal volume & issue: Vol. 24, no. 9
p. 7927

Abstract

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Genetic susceptibility may influence ischemic heart disease (IHD) predisposition and affect coronary blood flow (CBF) regulation mechanisms. The aim of this study was to investigate the association among single nucleotide polymorphisms (SNPs) of genes encoding for proteins involved in CBF regulation and IHD. A total of 468 consecutive patients were enrolled and divided into three groups according to coronary angiography and intracoronary functional tests results: G1, patients with coronary artery disease (CAD); G2, patients with coronary microvascular dysfunction (CMD); and G3, patients with angiographic and functionally normal coronary arteries. A genetic analysis of the SNPs rs5215 of the potassium inwardly rectifying channel subfamily J member 11 (KCNJ11) gene and rs1799983 of the nitric oxide synthase 3 (NOS3) gene, respectively encoding for the Kir6.2 subunit of ATP sensitive potassium (KATP) channels and nitric oxide synthase (eNOS), was performed on peripheral whole blood samples. A significant association of rs5215_G/G of KCNJ11 and rs1799983_T/T of NOS3 genes was detected in healthy controls compared with CAD and CMD patients. Based on univariable and multivariable analyses, the co-presence of rs5215_G/G of KCNJ11 and rs1799983_T/T of NOS3 may represent an independent protective factor against IHD, regardless of cardiovascular risk factors. This study supports the hypothesis that SNP association may influence the crosstalk between eNOS and the KATP channel that provides a potential protective effect against IHD.

Published in International Journal of Molecular Sciences

ISSN: 1661-6596 (Print); 1422-0067 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General); Science: Chemistry
Website: http://www.mdpi.com/journal/ijms

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