Leptin Causes Nitric-Oxide Independent Coronary Artery Vasodilation in Humans.

Matsuda, Keiji; Teragawa, Hiroki; Fukuda, Yukihiro; Nakagawa, Keigo; Higashi, Yukihito; Chayama, Kazuaki

doi:10.1291/hypres.26.147

Cited by 86 publications

(69 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, in rodents, leptin has been demonstrated to phosphorylate eNOS leading to NO release (Rodriguez et al 2007). Intra-arterial administration of leptin showed a similar vasoactive response independent of NO in humans (Matsuda et al 2003), including a vasorelaxing effect of leptin on smooth muscle cells (Momin et al 2006). Hence, acute hyperleptinaemia induces vasodilatory effects and seemingly contradicts the coexisting hypertension and increased leptin levels in obesity.…”

Section: Leptinmentioning

confidence: 99%

Role of adipokines in cardiovascular disease

Mattu¹,

Randeva²

2012

Journal of Endocrinology

251

203

View full text Add to dashboard Cite

The discovery of leptin in 1994 sparked dramatic new interest in the study of white adipose tissue. It is now recognised to be a metabolically active endocrine organ, producing important chemical messengers -adipokines and cytokines (adipocytokines). The search for new adipocytokines or adipokines gained added fervour with the prospect of the reconciliation between cardiovascular diseases (CVDs), obesity and metabolic syndrome. The role these new chemical messengers play in inflammation, satiety, metabolism and cardiac function has paved the way for new research and theories examining the effects they have on (in this case) CVD. Adipokines are involved in a 'good-bad', yin-yang homoeostatic balance whereby there are substantial benefits: cardioprotection, promoting endothelial function, angiogenesis and reducing hypertension, atherosclerosis and inflammation. The flip side may show contrasting, detrimental effects in aggravating these cardiac parameters.

show abstract

Section: Leptinmentioning

confidence: 99%

Role of adipokines in cardiovascular disease

Mattu¹,

Randeva²

2012

Journal of Endocrinology

251

203

View full text Add to dashboard Cite

show abstract

“…Leptin has also been shown to enhance platelet aggregation, which may lead to platelet adhesion [18]. Leptin levels are directly proportional to adiposity and leptin is capable of exerting a vasodilatory effect on coronary and resistance arteries through endothelium-dependant phosphorylation of eNOS at Ser1177 or directly through uncharacterized endothelium-independent mechanisms [124,125]. Interestingly, leptin levels are elevated in human obesity leading some scientists to postulate the existence of leptin resistance, with C reactive protein (CRP) identified as a possible source of disruption of intracellular leptin signaling [122].…”

Section: Inflammationmentioning

confidence: 99%

Obesity and vascular dysfunction

et al. 2008

View full text Add to dashboard Cite

One of the most profound challenges facing public health and public health policy in Western society is the increased incidence and prevalence of both overweight and obesity. While this condition can have significant consequences for patient mortality and quality of life, it can be further exacerbated as overweight/obesity can be a powerful stimulus for the development of additional risk factors for a negative cardiovascular outcome, including increased insulin resistance, dyslipidemia and hypertension. This manuscript will present the effects of systemic obesity on broad issues of vascular function in both afflicted human populations and in the most relevant animal models. Among the topics that will be covered are alterations to vascular reactivity (both dilator and constrictor responses), adaptations in microvascular network and vessel wall structure, and alterations to the patterns of tissue/organ perfusion as a result of the progression of the obese condition. Additionally, special attention will be paid to the contribution of chronic inflammation as a contributor to alterations in vascular function, as well as the role of perivascular adipose tissue in terms of impacting vessel behavior. When taken together, it is clearly apparent that the development of the obese condition can have profound, and frequently difficult to predict, impacts on integrated vascular function. Much of this complexity appears to have its basis in the extent to which other co-morbidities associated with obesity (e.g., insulin resistance) are present and exert contributing effects.

show abstract

“…17 In contrast to this, the leptininduced relaxation of human vessels was reported to be endothelium-and NO-independent. 18,19 It should, however, be mentioned that many studies focusing on direct vasodilator effects of leptin were performed using supraphysiological concentrations of the hormone (usually 10 nmol/L which equals 160 ng/mL) whereas at physiological leptin concentrations (10 ng/mL) few responses were noted (as discussed in 20 ). Despite the considerable interest in leptin, few studies have focused on the vascular effects of prolonged in vivo infusion of physiological concentrations (≈10 ng/mL plasma concentration) of leptin.…”

mentioning

confidence: 99%

Leptin Potentiates Endothelium-Dependent Relaxation by Inducing Endothelial Expression of Neuronal NO Synthase

Benkhoff

Loot

Pierson

et al. 2012

ATVB

View full text Add to dashboard Cite

Objective— Obesity is associated with hyperleptinemia but it is not clear whether leptin protects vascular function or promotes dysfunction. We therefore studied the consequences of hyperleptinemia in lean mice. Methods and Results— Wild-type and endothelial NO synthase (eNOS) −/− mice were infused with leptin (0.4 mg/kg per day, 7 days), and endothelium-dependent relaxation was studied in aortic segments. Leptin had no effect on acetylcholine-induced endothelium-dependent relaxation in normal wild-type mice but restored endothelium-dependent relaxation in wild-type mice treated with angiotensin II (0.7 mg/kg per day, 7 days) to induce endothelial dysfunction. Leptin also sensitized aortae from eNOS −/− mice to acetylcholine, an effect blocked by neuronal NOS (nNOS) inhibition and not observed in eNOS-nNOS double −/− mice. Consistent with these findings, leptin induced nNOS expression in murine and human vessels and human endothelial but not smooth muscle cells. Aortic nNOS expression was also induced in mice by a high-fat diet. Mechanistically, leptin increased endothelial Janus kinase 2 and signal transducer and activator of transcription 3 phosphorylation, and inhibition of Janus kinase 2 prevented nNOS induction in cultured cells and leptin-induced relaxations in eNOS −/− mice. Conclusion— Leptin induces endothelial nNOS expression, which compensates, in part, for a lack of NO production by eNOS to maintain endothelium-dependent relaxation.

show abstract

Leptin Causes Nitric-Oxide Independent Coronary Artery Vasodilation in Humans.

Cited by 86 publications

References 25 publications

Role of adipokines in cardiovascular disease

Role of adipokines in cardiovascular disease

Obesity and vascular dysfunction

Leptin Potentiates Endothelium-Dependent Relaxation by Inducing Endothelial Expression of Neuronal NO Synthase

Contact Info

Product

Resources

About