Diminished Global Arginine Bioavailability and Increased Arginine Catabolism as Metabolic Profile of Increased Cardiovascular Risk

Tang, W.H. Wilson; Wang, Zeneng; Cho, Leslie; Brennan, Danielle M.; Hazen, Stanley L.

doi:10.1016/j.jacc.2009.02.036

Cited by 186 publications

(181 citation statements)

References 27 publications

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“…HDL-C and triglyceride (TG) concentrations were measured on the Abbott ARCHITECT platform (Abbott Laboratories, Inc., Abbott Park, IL) as described (23,24). In the PAH population and a subset of control subjects, glucose, insulin levels, and highsensitivity C-reactive protein (CRP) were also measured with the Abbott ARCHITECT platform.…”

Section: Laboratory Measurementsmentioning

confidence: 99%

Plasma Levels of High-Density Lipoprotein Cholesterol and Outcomes in Pulmonary Arterial Hypertension

Heresi¹,

Aytekin²,

Newman³

et al. 2010

Am J Respir Crit Care Med

115

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Rationale: High-density lipoprotein cholesterol (HDL-C) promotes healthy vascular function, and it is decreased in insulin resistance. Insulin resistance predisposes to pulmonary vascular disease. Objectives: We hypothesized that HDL-C is associated with clinical outcomes in pulmonary arterial hypertension (PAH). Methods: Plasma HDL-C concentrations were measured in 69 patients with PAH (age, 46.7 6 12.9 yr; female, 90%) and 229 control subjects (age, 57 6 13 yr; female, 48%). Clinical outcomes of interest included hospitalization for PAH, lung transplantation, and all-cause mortality. Survival and time to clinical worsening curves were derived by the Kaplan-Meier method. Cox regression modeling of outcome versus HDL-C with individual covariate adjustments was performed. Measurement and Main Results: HDL-C was low in subjects with PAH compared with control subjects (median, interquartile range: PAH: 36, 29-40 mg/dl; control subjects: 49, 40-60 mg/dl; P , 0.001). An HDL-C level of 35 mg/dl discriminated survivors from nonsurvivors, with a sensitivity of 100% and specificity of 60%. After a median follow-up of 592 days, high HDL-C was associated with decreased mortality (hazard ratio for every 5-mg/dl increase in HDL-C, 0.643; 95% confidence interval, 0.504-0.822; P 5 0.001) and less clinical worsening (hazard ratio for every 5-mg/dl increase in HDL-C, 0.798; 95% confidence interval, 0.663-0.960; P 5 0.02). HDL-C remained a significant predictor of survival after adjusting for cardiovascular risk factors, C-reactive protein, indices of insulin resistance, and severity of PAH (all P , 0.05). Conclusions: Low plasma HDL-C is associated with higher mortality and clinical worsening in PAH. This association does not appear to be explained by underlying cardiovascular risk factors, insulin resistance, or the severity of PAH.

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Section: Laboratory Measurementsmentioning

confidence: 99%

Plasma Levels of High-Density Lipoprotein Cholesterol and Outcomes in Pulmonary Arterial Hypertension

Heresi¹,

Aytekin²,

Newman³

et al. 2010

Am J Respir Crit Care Med

115

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“…3 Low arginine bioavailability may further compromise NO generation due to NO synthase uncoupling. 9,16 Since we first reported an association of low global arginine bioavailability with mortality in SCD, 11 low arginine bioavailability has subsequently been linked to mortality risk in both malaria 17 and cardiovascular disease in general, 14 and represents a novel biomarker of vasculopathy independent of genotype. Intravascular hemolysis also has the potential to drive a pro-coagulant state, as NO has the properties of inhibiting platelet activation, tissue factor expression and thrombin generation.…”

Section: Mechanisms Of Vasculopathymentioning

confidence: 99%

Vascular risk assessment in patients with sickle cell disease

Morris¹

2010

Haematologica

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“…Patients with obstructive CAD had a lower global arginine bioavailability ratio (defined as arginine/[ornithine þ citrulline] versus plasma L-arginine levels) than those without obstructive CAD. 50 After adjusting for Framingham risk score, the lower global arginine availability ratio (but not L-arginine levels) and higher L-citrulline levels remained associated with the prevalence of obstructive CAD; global arginine availability ratio and ADMA showed a negative correlation. The global arginine availability ratio appears to serve as a more comprehensive concept of reduced NO synthetic capacity compared with systemic L-arginine levels.…”

Section: 23mentioning

confidence: 86%

“…The global arginine availability ratio appears to serve as a more comprehensive concept of reduced NO synthetic capacity compared with systemic L-arginine levels. Therefore, Tang et al 50 suggested that diminished arginine bioavailability ratio and high citrulline levels are associated with development of obstructive CAD and heightened long-term risk for major adverse cardiovascular events.…”

Section: 23mentioning

confidence: 99%

Nitric Oxide-Mediated Coronary Flow Regulation in Patients with Coronary Artery Disease: Recent Advances

Toda¹,

Tanabe²,

Nakanishi³

2011

Int J Angiol

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Nitric oxide (NO) formed via endothelial NO synthase (eNOS) plays crucial roles in the regulation of coronary blood flow through vasodilatation and decreased vascular resistance, and in inhibition of platelet aggregation and adhesion, leading to the prevention of coronary circulatory failure, thrombosis, and atherosclerosis. Endothelial function is impaired by several pathogenic factors including smoking, chronic alcohol intake, hypercholesterolemia, obesity, hyperglycemia, and hypertension. The mechanisms underlying endothelial dysfunction include reduced NO synthase (NOS) expression and activity, decreased NO bioavailability, and increased production of oxygen radicals and endogenous NOS inhibitors. Atrial fibrillation appears to be a risk factor for endothelial dysfunction. Endothelial dysfunction is an important predictor of coronary artery disease (CAD) in humans. Penile erectile dysfunction, associated with impaired bioavailability of NO produced by eNOS and neuronal NOS, is also considered to be highly predictive of ischemic heart disease. There is evidence suggesting an important role of nitrergic innervation in coronary blood flow regulation. Prophylactic and therapeutic measures to eliminate pathogenic factors inducing endothelial and nitrergic nerve dysfunction would be quite important in preventing the genesis and development of CAD.KEYWORDS: Nitric oxide, constitutive nitric oxide synthase, endothelial dysfunction, coronary blood flow, coronary artery disease, asymmetric dimethylarginine Coronary blood flow is regulated through complex adjustments in the arteriolar tone and resistance of the microcirculation. Impairment of microvascular function leads to organ dysfunction in any body system including the heart. Recent evidence supports the concept that the impairment of endothelial function is an upstream event in the pathophysiology of atherosclerosis, CAD, and myocardial infarction (MI). Nitric oxide (NO) liberated as a paracrine relaxant from the vascular endothelium is known to play a pivotal role in the modulation of microvascular tone and regional blood flow.1 In addition, NO inhibits platelet aggregation and adhesion, inhibits leukocyte adhesion and migration, and reduces vascular smooth muscle proliferation, thus leading to prevention of atherosclerosis. NO produced via neuronal NO synthase (nNOS) is released from Abundant and varied data from animal and human studies, performed over the course of more than two decades, indicate that depression of synthesis and bioavailability of NO in the endothelium participates in many cardiovascular diseases, including atherosclerosis, 4 coronary heart diseases, 5 stroke, 3 renal failure, 6 and hypertension 5,7 and also in insulin resistance and diabetes mellitus.8 Mechanisms underlying impairment of NO-mediated vasodilatation and blood flow increase include the downregulation of endothelial NOS (eNOS) and nNOS expressions, generation of NOS inhibitors and NO scavengers, and upregulation of vasoconstrictor substances, such as endothelin-1 (ET-1),...

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Diminished Global Arginine Bioavailability and Increased Arginine Catabolism as Metabolic Profile of Increased Cardiovascular Risk

Cited by 186 publications

References 27 publications

Plasma Levels of High-Density Lipoprotein Cholesterol and Outcomes in Pulmonary Arterial Hypertension

Plasma Levels of High-Density Lipoprotein Cholesterol and Outcomes in Pulmonary Arterial Hypertension

Vascular risk assessment in patients with sickle cell disease

Nitric Oxide-Mediated Coronary Flow Regulation in Patients with Coronary Artery Disease: Recent Advances

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