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Published on: September 29, 2017
Vasomotor and fibrinolytic effects of leptin in man
Manuel Gonzalez1, Simon Robinson2, Nicholas L Mills3
1Department of Public Health and Clinical Medicine, Section of Medicine, Umeå University, Umeå, Sweden.
Insights
Leptin, a hormone linked to cardiovascular disease, impairs blood vessel function. High leptin levels reduce vasodilation and affect fibrinolytic function in both healthy individuals and those with coronary artery disease.
Area of Science:
- Cardiovascular Science
- Endocrinology
- Vascular Biology
Background:
- Leptin, an adipocyte-derived hormone, is implicated in cardiovascular disease pathogenesis.
- The precise mechanisms linking leptin to cardiovascular issues, particularly its effects on the vascular endothelium, remain unclear.
Purpose of the Study:
- To investigate the impact of leptin on endothelial vasomotor and fibrinolytic function.
- To compare these effects in healthy volunteers and patients with coronary artery disease.
Main Methods:
- Assessed vascular effects of leptin by infusing recombinant human leptin in healthy volunteers.
- Measured vasomotor response using venous occlusion plethysmography.
- Analyzed circulating leptin levels in relation to endothelial dysfunction in coronary artery disease patients.
Main Results:
- Leptin infusion in healthy volunteers did not alter basal forearm blood flow or key fibrinolytic markers.
- Concomitant leptin infusion reduced drug-induced vasodilation and increased tissue plasminogen activator (tPA) activity.
- In coronary artery disease patients, higher leptin levels correlated with reduced vasodilation and increased tPA antigen and activity.
Conclusions:
- Intrabrachial leptin infusion did not affect basal vascular tone.
- Both acute and chronic hyperleptinemia were associated with impaired vasoreactivity in healthy individuals and coronary artery disease patients.
Objectives:
The adipocyte-derived hormone leptin has been associated with the pathogenesis of cardiovascular disease. The mechanisms underlying this association are unclear but may relate to effects on the vascular endothelium. Our aim was to explore the effects of leptin on endothelial vasomotor and fibrinolytic function in healthy volunteers and patients with coronary artery disease.
Design:
The vascular effects of leptin were assessed infusing recombinant human leptin in healthy volunteers during measuring vasomotor response by venous occlusion plethysmography. Additionally, circulating levels of leptin were analysed in relation to endothelial dysfunction in patients with established coronary artery disease.
Results:
In healthy male volunteers, intra-arterial infusion of recombinant human leptin (80, 800 and 8,000 ng/min; n = 10) did not affect basal forearm blood flow, plasma tissue plasminogen activator (tPA) or plasminogen activator inhibitor type 1 concentrations (all p > 0.05). However, during concomitant co-infusion with leptin (800 ng/min; n = 10), drug-induced vasodilatation was reduced (p = 0.001), and tPA activity increased (p = 0.002). In patients with coronary artery disease, those with the high plasma leptin levels had reduced drug-induced vasodilatation (p < 0.001), and increased net release of tPA antigen and activity (p < 0.001 and p = 0.03, respectively) compared to those with low levels. The study has been registered retrospectively at Clinical Trials with number NCT04374500.
Conclusion:
Intrabrachial leptin infusion did not affect the basal vascular tone, whereas acute and chronic hyperleptinemia was associated with blunted vasoreactivity in healthy volunteers, and in patients with coronary artery disease.

