Search for other papers by Samar A. Damiati in
Current site
Google Scholar
PubMed
PO Box 6781, Jeddah, 21452, Saudi Arabia
Search for other papers by Samir M. Khoja in
Current site
Google Scholar
PubMed
Abstract
Exposure to risk factors such as diabetes mellitus and hyperlipidemia decrease the bioavailability of endothelium-derived nitric oxide (NO) and impairs endothelium-dependent vasodilation. Circulating concentrations of an endogenous inhibitor of NO synthase, asymmetric dimethyl-L-arginine (ADMA), has been linked to endothelial dysfunction. It appears to be an independent risk factor for future cardiovascular events and total mortality. The purpose of this study is to investigate serum concentrations of ADMA correlate to diabetes mellitus and hyperlipidemia compared with the healthy subjects. A total of 300 subjects were recruited for the present study (100 normal healthy subjects, 52 males and 48 females); (100 diabetic patients, 51 males and 49 females); (100 hyperlipidemic patients, 50 males and 50 females). Serum concentrations of ADMA were measured with the use of ELISA. The concentration of ADMA were significantly higher (p < 0.001) in diabetic and hyperlipidemic patients in both sexes when compared with their matched control subjects. A positive correlation was obtained between ADMA and glucose of diabetic males (r = 0.40, p = 0.01) and females (r = 0.51, p = 0.01). In addition, a positive correlation was also obtained between ADMA and lipid profile of hyperlipidemic males (total cholesterol: r = 0.71, p = 0.01; triacylglycerol: r = 0.70, p = 0.01; low density lipoprotein cholesterol: r = 0.34, p = 0.05) and females (total cholesterol: r = 0.77, p = 0.01; triacylglycerol: r = 0.51, p = 0.01; low density lipoprotein cholesterol: r = 0.46, p = 0.01). The present study reveals that serum ADMA concentrations are elevated in disorders associated with vascular endothelial dysfunction such as diabetes mellitus and hyperlipidemia. However, endothelial dysfunction is considered as early event in the process of atherogenesis.
-
[1]. F. Abbasi T. Asagmi J. Cooke et al.2001 Plasma concentrations of asymmetric dimethylarginine are increased in patients with type 2 diabetes mellitus Amer. J. Cardiol. 88 1201–1203.
-
[2]. V. Achan M. Broadhead M. Malaki et al.2003 Asymmetric dimethylarginine causes hypertension and cardiac dysfunction in humans and is actively metabolized by dimethylarginine dimethylhydrolase Arteroscler. Thromb. Vasc. Biol. 23 1455–1459.
-
[3]. American Diabetes Association 2004 Diagnosis and Classification of Diabetes Mellitus Diab. Care. 27 5–10.
-
[4]. F. Arrigoni P. Vallance S. Haworth J. Leiper 2003 Metabolism of Asymmetric Dimethylarginines Is Regulated in the Lung Developmentally and With Pulmonary Hypertension Induced by Hypobaric Hypoxia Circ. 107 1195.
-
[5]. J. Bahl M. Matsuda R. A. DeFronzo R. Bressler 1997 In vitro and in vivo suppression of gluconeogenesis by inhibition of pyruvate carboxylase Biochem Pharmacol. 53 67–74.
-
[6]. R. Böger S. Bode-Böger J. Frölich 1996 The L-arginine — nitric oxide pathway: Role in atherosclerosis and therapeutic implications Atherosc. 127 1–11.
-
[7]. R. Böger S. Bode-Böger A. Szuba et al.1998 Asymmetric dimethylarginine (ADMA): A novel risk factor for endothelial dysfunction. Its role in hypercholesterolemia Circ. 98 1842–1847.
-
[8]. R. Böger K. Sydow J. Borlak et al.2000 LDL-cholesterol upreulates synthesis of asymmetrical dimethylarginine in human endothelial cells. Involvement of S-adenosylmethionine-dependent methyltransferases Circ. Res. 87 99–105.
-
[9]. R. Böger P. Vallance J. Cooke 2003 Asymmetric dimethylarginine (ADMA): a key regulator of nitric oxide synthase J. Atherosc. 4 1–3.
-
[10]. A. Ceriello 2006 Oxidative stress and diabetes-associated complications Endocr. Pract. 12 60–62.
-
[11]. J. Chan R. Böger S. Bode-Boger 2000 Asymmetric dimethylarginine increases mononuclear cell adhesiveness in hypercholesterolemic humans Arterioscler. Thromb. Vasc. Biol. 20 1040–1046.
-
[12]. J. Chapman A. Sposito 2008 Hypertension and dyslipidemia in obesity and insulin resistance: Pathophysiology, impact on atherosclerotic disease and pharmacotherapy Pharm. Thera. 117 354–373.
-
[13]. C. Chu S. Sherck K. Igawa et al.2002 Effects of free fatty acids on hepatic glycogenolysis and glucneogenesis in conscious dogs Am. J. Physiol. Endocrinol. Metab. 282 402–411.
-
[14]. M. Engler M. Engler M. Malloy et al.2003 Antioxidant Vitamins C and E Improve Endothelial Function in Children With Hyperlipidemia Circ. 108 1059.
-
[15]. A. Fard C. Tuck J. Donis et al.2000 Acute elevations of plasma asymmetric dimethylarginine and impaired endothelial function in response to a high-fat meal in patients with type 2 diabetes Arteriosc. Thromb. Vasc. Biol. 20 2039–2044.
-
[16]. A. Ito K. Egashira T. Narishige et al.2002 Angiotensin-converting enzyme activity is involved in the mechanism of increased endogenous nitric oxide synthase inhibitor in patients with type 2 diabetes mellitus Circ. J. 66 811–815.
-
[17]. K. Kauser V. Cunha R. Fitch et al.2000 Role of endogenous nitric oxide in progression of atherosclerosis in apolipoprotein E-deficient mice Am. J. Physiol. Heart Circ. Physiol. 278 H1679–H1685.
-
[18]. T. Kawata M. Daimon R. Hasegawa et al.2007 Effect of angiotensin-converting enzyme inhibitor on serum asymmetric dimethylarginine and coronary circulation in patients with type 2 diabetes mellitus Int. J. Card. 8 66.
-
[19]. A. Korish M. Arafah 2007 Catechin combined with vitamins C and E ameliorates insulin resistance (IR) and atherosclerotic changes in aged rats with chronic renal failure (CRF) Arch. Gerontol. Geriatrics. 46 25–39.
-
[20]. K. Krzyanowsha F. Mittermayer H. Kopp et al.2004 Weight loss reduced circulating asymmetric dimethylarginine concentrations in morbidly obese women J. Clin. Endocr. Metab. 89 6277–81.
-
[21]. B. Lewis 1988 The recognition and management of hyperlipidaemia in adults: A policy statement of the European Eur. Heart. J. 9 571–600.
-
[22]. X. Li Y. Zhou S. Zhou et al.2004 Effect of endogenous estrogen on endothelial function in women with coronary heart disease and its mechanism Clin. Chim. Acta. 339 183–188.
-
[23]. K. Lin A. Ito T. Asagami et al.2002 Impaired nitric oxide synthase pathway in diabetes mellitus: role of asymmetric dimethylarginine and dimethylarginine hydrolase Circ. 106 987–992.
-
[24]. P. Lundmn M. Eriksson M. Stuhlinger et al.2001 Mild-to-moderate hypertriglyceridemia in young men is associated with endothelial dysfunction and increased plasma concentrations of asymmetric dimethylrginine J. Amer. Coll. Cardiol. 38 111–116.
-
[25]. R. Maas 2005 Pharmacotherapies and their influence on asymmetric dimethylargine (ADMA) Vasc. Med. 10 49–57.
-
[26]. F. Mittermayer K. Krzyzanowska M. Exner et al.2006 Asymmetric Dimethylarginine Predicts Major Adverse Cardiovascular Events in Patients with Advanced Peripheral Artery Disease Arteriosc. Throm. Vasc. Biol. 26 2536.
-
[27]. F. Mittermayer J. Pleiner K. Krzyzanowska et al.2005 Regular physical exercise normalizes elevated asymmetrical dimethylarginine concentrations in patients with type 1 diabetes mellitus Wien Klin. Wochenschr. 117 816–820.
-
[28]. H. Miyazaki H. Matsuoka J. Cooke et al.1999 Endogenous nitric oxide synthase inhibitor. A novel marker of atherosclerosis J. Circ. 99 1141–1146.
-
[29]. R. Nijveldt T. Teerlink M. Siroen et al.2003 The liver is an important organ in the metabolism of asymmetrical dimethylarginine (ADMA) Clin. Nutr. 22 17–22.
-
[30]. P. Randle D. A. Priestman S. C. Mistry A. Arsland 1994 Glucose fatty acid interactions and the regulation of glucose disposal J. Cell Biochem. 55 1–11.
-
[31]. N. Rawal R. Rajpurohit M. Lischwe et al.1995 Structural specifity of substrate for S-adenosylmethionine: protein arginine N-methyltransferases Biochem. Biophys. Acta. 1248 11–18.
-
[32]. R. Schnabel S. Blankenberg E. Lubos et al.2005 Asymmetric dimethylarginine and the risk of cardiovascular events and death in patients with coronary artery disease: results from the atherogene study Circ. 97 e53–e59.
-
[33]. F. Schulze R. Maas R. Freese et al.2005 Determination of a reference value for NG, NG -dimethyl-L-arginine in 500 subjects Eur. J. Clin. Invest. 35 622–626.
-
[34]. M. Stuhlinger P. Tsao J. Her et al.2001 Homocysteine impairs the nitric oxide synthase pathway: role of asymmetric dimethylarginine Circ. 104 2569–2575.
-
[35]. A. Surdacki E. Stochmal M. Szurkowska et al.2007 Nontraditional atherosclerotic risk factors and extent of coronary atherosclerosis in patients with combined impaired fasting glucose and impaired glucose tolerance Metab. Clin. Exp. 56 77–86.
-
[36]. L. Tarnow P. Hovind T. Teerlink et al.2004 Elevated Plasma Asymmetric Dimethylarginine as a Marker of Cardiovascular Morbidity in Early Diabetic Nephropathy in Type 1 Diabetes Diab. Care. 27 765–769.
-
[37]. P. Vallance J. Leiper 2004 Cardiovascular biology of the asymmetric dimethylarginine: dimethylarginine dimethyl-aminohydrolase pathway Arterioscler. Thromb. Vasc. Biol. 24 1023.
-
[38]. P. Vallance J. Leiper 2005 Asymmetric Dimethylarginine and Kidney Disease — Marker or Mediator? J. Am. Soc. Nephrol. 16 2254–2256.
-
[39]. P. Vallance A. Leone A. Calver et al.1992 Endogenous dimethyl-arginine as an inhibitor of nitric oxide synthesis J. Cardiovasc. Pharmacol. 20 60–62.
-
[40]. M. Verhoeven M. Hemelaar T. Teerlink et al.2007 Effects of intranasal versus oral hormone therapy on asymmetric dimethylarginine in healthy postmenopausal women: A randomized study Atherosc. 195 181–188.
-
[41]. J. Yoo S. Lee 2001 Elevated levels of plasma homocysteine and asymmetric dimethylarginine in elderly patients with stroke Atherosc. 158 425–430.
| Clinical and Experimental Medical Journal | |
|---|---|
| Language | English |
| Size | |
| Year of Foundation |
2007 |
| Publication Programme |
ceased |
| Volumes per Year |
|
| Issues per Year |
|
| Publisher | Akadémiai Kiadó |
| Publisher's Address |
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245 |
| Responsible Publisher |
Chief Executive Officer, Akadémiai Kiadó |
| ISSN | 2060-6249 (Print) |
| ISSN | 2060-968X (Online) |
Monthly Content Usage
| Abstract Views | Full Text Views | PDF Downloads | |
|---|---|---|---|
| Nov 2024 | 38 | 0 | 0 |
| Dec 2024 | 22 | 0 | 0 |
| Jan 2025 | 39 | 0 | 0 |
| Feb 2025 | 36 | 0 | 0 |
| Mar 2025 | 35 | 0 | 0 |
| Apr 2025 | 30 | 0 | 0 |
| May 2025 | 2 | 0 | 0 |
1st Congress of Fatty Liver and Metabolic Syndrome
From Basic Science to the Clinical Praxis
Copyright Akadémiai Kiadó AKJournals is the trademark of Akadémiai Kiadó's journal publishing business branch.