MFAP4-Deficiency Aggravates Age-Induced Changes in Resistance Artery Structure, While Ameliorating Hypertension

Area of Science:

• Vascular Biology
• Cardiovascular Physiology
• Extracellular Matrix Research

Background:

• Abnormalities in resistance arteries are implicated in aging and hypertension.
• Microfibrillar-associated protein 4 (MFAP4) deficiency has shown protective effects against arterial remodeling.
• The role of MFAP4 in age- and hypertension-related arterial changes requires further investigation.

Purpose of the Study:

• To investigate the impact of MFAP4 deficiency on extracellular matrix composition and arterial stiffening in aging and hypertensive conditions.
• To test the hypothesis that MFAP4 deficiency reduces age- and hypertension-dependent arterial changes.

Main Methods:

• Mesenteric arteries from aged and angiotensin II-infused hypertensive mice with and without MFAP4 were analyzed.
• Two-photon microscopy quantified elastin and collagen.
• Wire- and pressure-myography assessed arterial stiffness, myogenic tone, and responses to vasoconstrictors.

Main Results:

• MFAP4 deficiency increased collagen and elastin fragmentation in aged arteries but did not alter stiffness.
• MFAP4-deficient mice showed reduced diastolic pressure during angiotensin II-induced hypertension.
• MFAP4 deficiency reduced arterial stiffness and improved vasoconstrictor response in hypertensive arteries.

Conclusions:

• MFAP4 deficiency alters the elastin/collagen ratio in aging arteries without affecting stiffness.
• MFAP4 deficiency reduces resistance artery stiffness and ameliorates angiotensin II-induced hypertension.