Effects of common variations of NOS3 and CAV1 genes on hypercholesterolemic profile in coronary heart disease

Year 2019, Volume: 49 Issue: 2, 53 - 60, 01.08.2019

Serap İlikay Ender Coşkunpınar Özlem Kurnaz-gömleksiz Zehra Buğra Allison P. Eronat Oğuz Öztürk Hülya Yılmaz-aydoğan

Abstract

DOI: 10.26650/IstanbulJPharm.2019.18010

Caveolin-1 (CAV-1) plays a crucial role in
endothelial-nitric oxide synthase (eNOS) enzymatic activity. Therefore, CAV-1
and eNOS interactions have a significant impact on endothelial dysfunction,
cholesterol levels, and atherosclerosis. We investigated the critical
variations in NOS3 and CAV1 genes in this case–control study to determine the
relations between the coronary heart disease (CHD) risk factors. The
NOS3-rs1799983, CAV-1 rs3840634, and rs3807990 variations were analyzed in 76
CHD patients and 91 controls using the polymerase chain reaction. Mean serum
Total-cholesterol levels were significantly higher in CHD patients with the
CAV-1 rs3807990-T allele than in patients with CC genotype (p=0.017). There was
a statistically significant correlation between the rs3807990-T allele and
hypercholesterolemia in the CHD group (p=0.008). The multivariate analysis
confirmed that the CAV-1 rs3807990-T allele (p=0.011) is a risk factor for
hypercholesterolemia. Moreover, the serum HDL-Cholesterol level was detected to
be higher in patients carrying both CAV1-rs3807990-T and NOS3-rs1799983-T
alleles than those with the CAV-1 rs3807990-CC/NOS3-rs1799983-GG genotype
subgroup (p=0.013). These results suggested that the genetic variations of
CAV-1 rs3807990 and NOS3-rs1799983 may contribute to the increased
hypercholesterolemia risk and thus on the development of CHD.

Cite this article as: İlikay S, Coşkunpınar
E, Kurnaz-Gömleksiz Ö, Buğra Z, Eronat AP, Öztürk O, Yılmaz-Aydoğan H (2019).
Effects of common variations of NOS3 and CAV1 genes on hypercholesterolemic
profile in coronary heart disease. Istanbul J Pharm 49 (2): 53-60.

Keywords

Cav1, NOS3, gene, hypercholesterolemia, lipid, CHD

References

• Atochin DN, Wang A, Liu VW, Critchlow JD, Dantas AP, Looft-Wilson R, Murata T, Salomone S, Shin HK, Ayata C, Moskowitz MA, Michel T, Sessa WC, Huang PL (2007). The phosphorylation state of eNOS modulates vascular reactivity and outcome of cerebral ischemia in vivo. J Clin Invest 117: 1961-1967. Blair A, Shaul PW, Yuhanna IS, Conrad PA, Smart EJ (1999). Oxidized low-density lipoprotein displaces endothelial nitric-oxide synthase (eNOS) from plasmalemmal caveolae and impairs eNOS activation. J Biol Chem 274: 32512-32519. Carey RM, Schoeffel CD, Gildea JJ, Jones JE, McGrath HE, Gordon LN, Park MJ, Sobota RS, Underwood PC, Williams J, Sun B, Raby B, Lasky-Su J, Hopkins PN, Adler GK, Williams SM, Jose PA, Felder RA (2012). Salt sensitivity of blood pressure is associated with polymorphisms in the sodium-bicarbonate cotransporter. Hypertension 60: 1359-1366. Casas JP, Bautista LE, Humphries SE, Hingorani AD (2004). Endothelial nitric oxide synthase genotype and ischemic heart disease: meta-analysis of 26 studies involving 23028 subjects. Circulation 109: 1359-1365. Chen PF, Tsai AL, Berka V, Wu K (1996). Endothelial nitric-oxide synthase evidence for bidomain structure and successful reconstitution of catalytic activity from two separate domains generated by a baculovirus expression system. J Biol Chem 271: 14631-14635. Chen S, Wang C, Wang X, Xu C, Wu M, Wang P, Tu X, Wang QK (2015). Significant Association between CAV1 Variant rs3807989 on 7p31 and Atrial Fibrillation in a Chinese Han Population. J Am Heart Assoc 4: e001980. Colombo MG, Andreassi MG, Paradossi U, Botto N, Manfredi S, Masetti S, Rossi G, Clerico A, Biagini A (2002). Evidence for association of a common variant of the endothelial nitric oxide synthase gene (Glu298→Asp polymorphism) to the presence, extent, and severity of coronary artery disease. Heart 87: 525-528. Conde MC, Ramirez-Lorca R, Lopez-Jamar JM, Molero E, Ramirez-Armengol JA, Moreno Nogueira JA, Pascual MH, Ruiz A, Martin-Cordova CG, Real LM, Royo JL (2006). Genetic analysis of caveolin-1 and eNOS genes in colorectal cancer. Oncol Rep 16: 353-359. Couet J, Li S, Okamoto T, Ikezu T, Lisanti MP (1997). Identification of peptide and protein ligands for the caveolin-scaffolding domain. Implications for the interaction of caveolin with caveolae-associated proteins. J Biol Chem 272: 6525-6533. Drab M, Verkade P, Elger M, Kasper M, Lohn M, Lauterbach B, Menne J, Lindschau C, Mende F, Luft FC, Schedl A, Haller H, Kurzchalia TV (2001). Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene-disrupted mice. Science 293: 2449-2452. Fedele F, Mancone M, Chilian WM, Severino P, Canali E, Logan S, De Marchis ML, Volterrani M, Palmirotta R, Guadagni F (2013). Role of genetic polymorphisms of ion channels in the pathophysiology of coronary microvascular dysfunction and ischemic heart disease. Basic Res Cardiol 108: 387. Frank PG, Lisanti MP (2004). Caveolin-1 and caveolae in atherosclerosis: differential roles in fatty streak formation and neointimal hyperplasia. Curr Opin Lipidol 15: 523-529. Frank PG, Cheung MW, Pavlides S, Llaverias G, Park DS, Lisanti MP (2006). Caveolin-1 and regulation of cellular cholesterol homeostasis. Am J Physiol Heart Circ Physiol 291: H677-H686. Freedman JE, Sauter R, Battinelli EM, Ault K, Knowles C, Huang PL, Loscalzo J (1999). Deficient platelet derived nitric oxide and enhanced hemostasis in mice lacking the NOSIII gene. Circ Res 84: 1416-1421. Foy CA, Grant PJ (1997). Genes and the development of vascular disease. Postgrad Med J 73: 271-278. Granath B, Taylor RR, Van Bockxmeer FM, Mamotte CD (2001). Lack of evidence for association between endothelial nitric oxide synthase gene polymorphisms and coronary artery disease in the Australian Caucasian population. J Cardiovasc Risk 8: 235-241. Grilo A, Fernandez ML, Beltrán M, Ramirez-Lorca R, González MA, Royo JL, Gutierrez-Tous R, Morón FJ, Couto C, Serrano-Rios M, Saez ME, Ruiz A, Real LM (2006). Genetic analysis of CAV1 gene in hypertension and metabolic syndrome. Thromb Haemost 95: 696-701. Hadi HAR, Suwaidi JA (2007). Endothelial dysfunction in diabetes mellitus. Vasc Health Risk Manag 3: 853-876. Hassan GS, Jasmin JF, Schubert W, Frank PG, Lisanti MP (2004). Caveolin-1 deficiency stimulates neointima formation during vascular injury. Biochemistry 43: 8312-8321. Hingorani AD, Liang CF, Fatibene J, Lyon A, Monteith S, Parsons A, Haydock S, Hopper RV, Stephens NG, O’Shaughnessy KM, Brown MJ (1999). A Common Variant of the Endothelial Nitric Oxide Synthase (Glu2983Asp) Is a Major Risk Factor for Coronary Artery Disease in the UK. Circulation 100: 1515-1520. Huang PL, Huang Z, Mashimo H, Bloch KD, Moskowitz MA, Bevan JA, Fishman MC (1995). Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature 377: 239-242. Huang PL (2000). Lessons learned from nitric oxide synthase knockout animals. Semin Perinatol 24: 87-90. Huang Z, Huang PL, Ma J, Meng W, Ayata C, Fishman MC, Moskowitz MA (1996). Enlarged infarcts in endothelial nitric oxide synthase knockout mice are attenuated by nitro-L-arginine. J Cereb Blood Flow Metab 16: 981-987. Joshi MS, Mineo C, Shaul PW, Bauer JA (2007). Biochemical consequences of the NOS3 Glu298Asp variation in human endothelium: altered caveolar localization and impaired response to shear. FASEB J 21: 2655-2663. Ju H, Zou R, Venema VJ, Venema RC (1997). Direct interaction of endothelial nitric-oxide synthase and caveolin-1 inhibits synthase activity. J Biol Chem 272: 18522-18525. Karvonen J, Kauma H, Kervinen K, Rantala M, Ikäheimo M, Päivänsalo M Savolainen MJ, Kesäniemi YA (2002). Endothelial nitric oxide synthase gene Glu298Asp polymorphism and blood pressure, left ventricular mass and carotid artery atherosclerosis in a population-based cohort. J Intern Med 251: 102-110. Lahera V, Goicoechea M, de Vinuesa SG, Miana M, de las Heras N, Cachofeiro V, Luño J (2007). Endothelial dysfunction, oxidative stress and inflammation in atherosclerosis: beneficial effects of statins. Curr Med Chem 14: 243-248. Lefer DJ, Jones SP, Girod WG, Baines A, Grisham MB, Cockrell AS, Huang PL, Scalia R (1999). Leukocyte-endothelial cell interactions in nitric oxide synthase-deficient mice. Am J Physiol 276: H1943-H1950. Lusis AJ (2000). Atherosclerosis. Nature 407: 233-241. Marsden PA, Heng HH, Scherer SW, Stewart RJ, Hall AV, Shi XM, Tsui LC, Schappert KT (1993). Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene. J Biol Chem 268: 17478-17488. Puglielli L, Rigotti A, Greco AV, Santos MJ, and Nervi F (1995). Sterol carrier protein-2 is involved in cholesterol transfer from the endoplasmic reticulum to the plasma membrane in human fibroblasts. J Biol Chem 270: 18723-18726. Razani B, Engelman JA, Wang XB, Schubert W, Zhang XL, Marks CB, Macaluso F, Russell RG, Li M, Pestell RG, Di Vizio D, Hou H Jr, Kneitz B, Lagaud G, Christ GJ, Edelmann W, Lisanti MP (2001). Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities. J Biol Chem 276: 38121-38138. Razani B, Combs TP, Wang XB, Frank PG, Park DS, Russell RG, Li M, Tang B, Jelicks LA, Scherer PE, Lisanti MP (2001). Caveolin-1 deficient mice are lean, resistant to diet-induced obesity, and show hyper-triglyceridemia with adipocyte abnormalities. J Biol Chem 277: 8635-8647. Schwencke C, Schmeisser A, Walter C, Wachter R, Pannach S, Weck B, Braun-Dullaeus RC, Kasper M, Strasser RH (2005). Decreased Caveolin-1 in atheroma: loss of antiproliferative control of vascular smooth muscle cells in atherosclerosis. Cardiovasc Res 68: 128-135. Shyu HY, Chen MH, Hsieh YH, Shieh JC, Yen LR, Wang HW, Cheng CW (2017). Association of eNOS and Cav-1 gene polymorphisms with susceptibility risk of large artery atherosclerotic stroke. PLoS One 12: e0174110. Smart EJ, Ying Y, Donzell WC, Anderson RG (1996). A role for caveolin in transport of cholesterol from endoplasmic reticulum to plasma membrane. J Biol Chem 271: 29427-29435. Venema RC, Sayegh H, Kent JD, Harrison DG (1996). Identification, characterization and comparison of the calmodulin-binding domains of the endothelial and inducible nitric oxide synthases. J Biol Chem 271: 6435-6440. Williams TM, Lisanti MP (2004). The caveolin proteins. Genome Biol 5: 214. Yoshimura M, Yasue H, Nakayama M, Shimasaki Y, Sumida H, Sugiyama S, Kugiyama K, Ogawa H, Ogawa Y, Saito Y, Miyamoto Y, Nakao K (1998). A missense glu298-to-asp variant in the endothelial nitric oxide synthase gene is associated with coronary spasm in the Japanese. Hum Genet 103: 65-69.