Cellular-scale sex differences in extracellular matrix remodeling by valvular interstitial cells

Area of Science:

• Cardiovascular Biology
• Extracellular Matrix Research
• Sex Differences in Disease

Background:

• Calcific aortic valve disease (CAVD) affects males twice as often as females.
• Female patients with CAVD exhibit greater valve fibrosis than males.
• Fibrosis involves an imbalance in extracellular matrix (ECM) production and degradation.

Purpose of the Study:

• To characterize sex-based differences in ECM production and remodeling by valvular interstitial cells (VICs).
• To understand the contribution of VICs to sexual dimorphism in CAVD fibrosis.

Main Methods:

• Assessed gene and protein expression of myofibroblastic markers, ECM components, matrix metalloproteinases (MMPs), and tissue inhibitors of MMPs (TIMPs) in male and female VICs.
• Measured overall metabolic activity and collagenase/gelatinase activity.
• Utilized qRT-PCR and western blot techniques.

Main Results:

• Male VICs produced higher levels of myofibroblastic markers.
• Female VICs demonstrated greater metabolic activity and collagen production.
• Females generally showed higher MMP expression, while males had greater collagenase and gelatinase activity. No sex differences in TIMP production were observed.

Conclusions:

• Significant sex differences exist in VIC-mediated ECM remodeling.
• These cellular differences may explain the observed sexual dimorphism in CAVD fibrosis and ECM structure.