Adipocyte Calpain-2 Deficiency Reduces Obesity-Accelerated Abdominal Aortic Aneurysm Formation in Mice

Area of Science:

• Biochemistry
• Cardiovascular Biology
• Obesity Research

Background:

• Abdominal adiposity increases the risk of abdominal aortic aneurysm (AAA) development.
• Calpains, calcium-dependent proteases, are implicated in AAA pathogenesis and adipose tissue inflammation.
• Previous studies showed calpain-2 deficiency mitigates angiotensin II (AngII)-induced AAA in hypercholesterolemic mice.

Purpose of the Study:

• To investigate the role of adipocyte-specific calpain-2 in obesity-accelerated AAA development.
• To determine if depleting calpain-2 in adipocytes affects AAA formation in diet-induced obese mice.

Main Methods:

• Utilized calpain-2 floxed mice crossed with tamoxifen-inducible Cre recombinase under ubiquitous (chicken β-actin) or adipocyte-specific (Adipoq) promoters.
• Administered angiotensin II (AngII) to diet-induced obese mice to induce AAA.
• Assessed AAA formation, incidence, aortic medial elastin fragmentation, collagen disruption, and periaortic leukocytic infiltration.

Main Results:

• Calpain-2 protein is highly expressed in the periaortic adipose tissue of mice with AngII-induced AAAs.
• Both ubiquitous and adipocyte-specific depletion of calpain-2 significantly suppressed AngII-induced AAA formation in obese mice.
• Calpain-2 deficiency reduced AAA incidence and prevented aortic structural damage, including elastin fragmentation and collagen disruption, and decreased leukocytic accumulation.

Conclusions:

• Adipocyte-derived calpain-2 plays a critical role in the development of AngII-induced AAA in diet-induced obese mice.
• Targeting adipocyte calpain-2 may represent a therapeutic strategy for preventing AAA in obese individuals.