Elevated blood pressure in transgenic lipoatrophic mice and altered vascular function

Area of Science:

• Cardiovascular Biology
• Endocrinology
• Vascular Physiology

Background:

• Perivascular adipose tissue (PVAT) influences vascular tone and function.
• Lipoatrophy, a condition characterized by fat loss, can impact metabolic and cardiovascular health.

Purpose of the Study:

• To investigate the role of perivascular fat in the control of vascular function and blood pressure regulation.
• To elucidate the mechanisms underlying blood pressure elevation in lipoatrophic mice.

Main Methods:

• Utilized lipoatrophic A-ZIP/F1 transgenic mice and wild-type (WT) littermates.
• Assessed blood pressure, vascular contractility in response to various agonists (phenylephrine, serotonin, Angiotensin II).
• Analyzed expression of Angiotensin II receptors and investigated the role of a perivascular fat-derived relaxation factor.

Main Results:

• A-ZIP/F1 mice exhibited higher blood pressure compared to WT mice.
• The absence of perivascular fat in A-ZIP/F1 mice reduced the inhibitory effect on vascular contraction and impaired relaxation factor release.
• Vascular Angiotensin II type 1 receptor expression was upregulated in A-ZIP/F1 mice, contributing to enhanced contractile responses.
• Treatment with an Angiotensin II type 1 receptor antagonist normalized blood pressure in A-ZIP/F1 mice.

Conclusions:

• Perivascular fat absence enhances vascular contractility and contributes to hypertension in lipoatrophic mice.
• Upregulation of vascular Angiotensin II type 1 receptors is a key mechanism in this blood pressure elevation.
• Targeting Angiotensin II type 1 receptors may be a therapeutic strategy for hypertension associated with lipoatrophy.