Change search
ReferencesLink to record
Permanent link

Direct link
Leptin and endothelial function in the elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
Uppsala Univ, Dept Med, Uppsala, Sweden.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
2013 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 228, no 2, 485-490 p.Article in journal (Refereed) Published
Abstract [en]

Background: Leptin levels are elevated in obese humans. Several studies have shown an association between hyperleptinemia and development of atherosclerosis and cardiovascular disease (CVD), but the relationship between leptin and vascular function remains unclear.

Aim: To evaluate associations between circulating plasma leptin and measures of vascular function in a large sample of elderly individuals from the community.

Methods: This cross-sectional study included 1016 subjects aged 70 (50% women) from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). The invasive technique forearm plethysmography with intra-arterial infusions of acetylcholine and sodium nitroprusside was used for estimation of endothelial dependent vasodilatation (EDV) and endothelial independent vasodilatation (EIDV), respectively, in resistance arteries, and the non-invasive technique ultrasound assessed flow mediated vasodilation (FMD) in conduit arteries. The aortic augmentation index (AoAI), a surrogate measure of arterial stiffness, was evaluated by pulse wave analysis. Associations of vascular function, arterial stiffness and blood pressure with leptin were explored.

Results: In sex-adjusted models, high levels of leptin were inversely associated with EDV and EIDV. These associations remained after stratification for sex, traditional risk factors of CVD and insulin resistance, but were attenuated after taking a measure of obesity (body mass index) into account. In addition, leptin associated with arterial stiffness and systolic and diastolic blood pressure.

Conclusion: Hyperleptinemia associated inversely with vasodilatation in resistance arteries. Furthermore, hyperleptinemia associated with arterial stiffness and hypertension. These associations were attenuated after adjusting for body mass index suggesting that leptin may be the mediator between obesity and impaired vascular function. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

Place, publisher, year, edition, pages
Elsevier, 2013. Vol. 228, no 2, 485-490 p.
National Category
Cardiac and Cardiovascular Systems
URN: urn:nbn:se:umu:diva-73561DOI: 10.1016/j.atherosclerosis.2013.03.018ISI: 000319037200031OAI: diva2:632702
Available from: 2013-06-25 Created: 2013-06-25 Last updated: 2014-05-07Bibliographically approved
In thesis
1. The role of leptin in endothelial dysfunction and cardiovascular disease
Open this publication in new window or tab >>The role of leptin in endothelial dysfunction and cardiovascular disease
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Betydelsen av fetma och fetvävnadsassocierat hormon leptin för endotelial dysfunktion och kardiovaskulär disease
Abstract [en]

Objective:  Obesity has become the leading cause of mortality worldwide; however, the fundamental pathophysiology underlying this association remains unclear. The discovery of adipokines, i.e., cytokines produced by adipose cells (adipocytes), revealed that adipose tissue is a highly endocrine organ, thus opening new lines of investigation. The prototypical adipokine leptin increases in obesity, and leptin receptors are found in vascular cells. However, results are contradictory regarding the role of leptin in vascular and endothelial functions. Leptin has been shown to elicit vasodilatation, but has also been linked with atherosclerotic and thrombotic disease. The main aim of the present thesis was to study the association of circulating levels of leptin with markers of endothelial function, and to analyze the effects of leptin infusion in vivo  on vasomotor function and endogenous fibrinolysis.

Material:  Four associative studies and two interventional studies were conducted. The former included DISARM (studies 1 and 2), the PIVUS study (study 3), and the Scottish post-infarction study (study 4). The DISARM studies and study 4, respectively, recruited 20 men and 83 men and women with stable ischemic heart disease. Study 3 included a random sample of 1016 subjects (54% women, 70 years old) living in the community of Uppsala, Sweden. For the interventional studies (studies 5 and 6), 10 healthy men were recruited for each study.

Methods:  In all studies, endothelial function was estimated based on forearm blood flow (FBF) as measured by strain-gauge venous occlusion plethysmography, at rest or during infusion of vasodilators. In study 3, additional measurement techniques were used, such as brachial ultrasound flow-mediated dilation (FMD) and the aortic augmentation index (AoAIx) by tonometry in the radial artery. Fibrinolytic status was estimated based on basal and stimulated levels of tissue plasminogen activator antigen (t-PA), and by assessment of the endothelial release of t-PA (net t-PA release). Plasma leptin levels were measured by radioimmunoassay. In the associative studies, endothelial function and fibrinolytic status were related to circulating plasma leptin levels. In the experimental studies, exogenous leptin was administered in the brachial artery and endothelial function was assessed by strain-gauge plethysmography

Results:  In elderly men and women, leptin was independently associated with decreased endothelial-dependent and -independent vasodilatation, reflecting disturbed endothelial function in resistance vessels. This association was attenuated after adjustment for BMI, and when analyzed among subjects with high plasma leptin levels. FMD (a measure of endothelial function in conduit vessels) was not associated with leptin. Exogenous leptin infusion did not alter vasomotor tone, but the endothelium-dependent and -independent vasodilatation was impaired during concomitant infusion of leptin and vasodilators. Infused leptin in the forearm did not affect blood pressure or pulse rate. Chronic hyperleptinemia, but not acutely induced hyperleptinemia, was associated with release of endothelial tissue plasminogen activator (net t-PA).

Conclusions:  In humans, leptin was associated with impaired vasodilatation. However, this relationship was blunted after adjustment for BMI, suggesting that leptin could be the mediator between obesity and impaired vascular function. Furthermore, the observed lack of association in hyperleptinemic subjects may reflect a state of leptin resistance. The experimental result showing attenuated vascular reactivity following leptin infusion is in accordance with the results of the associative studies. The augmented net t-PA release in patients with chronic hyperleptinemia may indicate a state of “vascular activation,” which was not observed in healthy endothelium during a short period of leptin infusion. This thesis addresses several controversial issues regarding the action of leptin on vascular tissue in humans. The final results indicate that the in vivo action of leptin on vascularity is complex and mediated by several mechanisms. Our findings suggest that leptin is an important mediator between obesity and endothelial dysfunction, and should stimulate further investigation of this matter.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2013. 116 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1586
leptin, obesity, endothelial dysfunction, cardiovascular disease
National Category
Cardiac and Cardiovascular Systems
Research subject
urn:nbn:se:umu:diva-79823 (URN)978-91-7459-703-5 (ISBN)
Public defence
2013-09-27, E04, by 6E, Norrlands universitetssjukhus, Umeå, 13:00 (Swedish)
Manuel Cruz Gonzalez
Swedish Heart Lung Foundation
Available from: 2013-09-06 Created: 2013-09-03 Last updated: 2013-09-06Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Gonzalez, ManuelSöderberg, Stefan
By organisation
In the same journal
Cardiac and Cardiovascular Systems

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 90 hits
ReferencesLink to record
Permanent link

Direct link