Apr 15, 2020

Inducible Depletion of Calpain-2 Mitigates Abdominal Aortic Aneurysm in Mice

BioRxiv : the Preprint Server for Biology
L. MuniappanVenkateswaran Subramanian

Abstract

BACKGROUND: Cytoskeletal structural proteins maintain cell structural integrity by bridging extracellular matrix (ECM) with contractile filaments. During AAA development, (i) aortic medial degeneration is associated with loss of smooth muscle cell (SMC) integrity, and (ii) fibrogenic mesenchymal cells (FMSCs) mediates ECM remodeling. Calpains cleave cytoskeletal proteins that maintain cell structural integrity. Pharmacological inhibition of calpains exert beneficial effects on Angiotensin II (AngII)-induced AAAs in low density receptor deficient (LDLR-/-) mice. OBJECTIVES: To evaluate the functional contribution of FMSCs-derived calpain-2 on (i) cytoskeletal structural protein and ECM alterations, and (ii) AAA progression. METHODS: Calpain-2 protein, and cytoskeletal protein (e.g. filamin or talin) fragmentation in human and mice AAA tissues were assessed by immunohistochemical and western blot analyses. LDLR-/- mice that were either inducible-whole body or FMSC-specific calpain-2 deficient were fed a fat-enriched diet and infused with AngII for 4 weeks. The association of cytoskeletal protein to ECM was evaluated using aortic SMCs, in vitro. In addition, the effect of calpain-2 deficiency on the stability of established AAA wa...Continue Reading

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Mentioned in this Paper

Gene Polymorphism
Meiotic Cell Cycle
Genome
Genes
Segmental Duplications, Genomic
Recombination, Genetic
Phylogenetic Analysis
House mice
Visual Suppression
CWC22 gene

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