Format

Send to

Choose Destination
J Atheroscler Thromb. 2018 Jan 1;25(1):1-15. doi: 10.5551/jat.RV17008. Epub 2017 Aug 17.

Dysregulation of Calpain Proteolytic Systems Underlies Degenerative Vascular Disorders.

Author information

1
Department of Biochemistry, Showa University School of Medicine.

Abstract

Chronic vascular diseases such as atherosclerosis, aneurysms, diabetic angiopathy/retinopathy as well as fibrotic and proliferative vascular diseases are generally complicated by the progression of degenerative insults, which are characterized by endothelial dysfunction, apoptotic/necrotic cell death in vascular/immune cells, remodeling of extracellular matrix or breakdown of elastic lamella. Increasing evidence suggests that dysfunctional calpain proteolytic systems and defective calpain protein metabolism in blood vessels contribute to degenerative disorders. In vascular endothelial cells, the overactivation of conventional calpains consisting of calpain-1 and -2 isozymes can lead to the disorganization of cell-cell junctions, dysfunction of nitric oxide synthase, sensitization of Janus kinase/signal transducer and activator of transcription cascades and depletion of prostaglandin I2, which contributes to degenerative disorders. In addition to endothelial cell dysfunctions, calpain overactivation results in inflammatory insults in macrophages and excessive fibrogenic/proliferative signaling in vascular smooth muscle cells. Moreover, calpain-6, a non-proteolytic unconventional calpain, is involved in the conversion of macrophages to a pro-atherogenic phenotype, leading to the pinocytotic deposition of low-density lipoprotein cholesterol in the cells. Here, we discuss the recent progress that has been made in our understanding of how calpain contributes to degenerative vascular disorders.

KEYWORDS:

Calpastatin; Extracellular matrix; Oxidative stress; Pathological angiogenesis; Vascular inflammation

PMID:
28819082
PMCID:
PMC5770219
DOI:
10.5551/jat.RV17008
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for J-STAGE, Japan Science and Technology Information Aggregator, Electronic Icon for PubMed Central
Loading ...
Support Center