RGD Reference Report - Calpain-1 regulation of matrix metalloproteinase 2 activity in vascular smooth muscle cells facilitates age-associated aortic wall calcification and fibrosis. - Rat Genome Database

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Calpain-1 regulation of matrix metalloproteinase 2 activity in vascular smooth muscle cells facilitates age-associated aortic wall calcification and fibrosis.

Authors: Jiang, Liqun  Zhang, Jing  Monticone, Robert E  Telljohann, Richard  Wu, James  Wang, Mingyi  Lakatta, Edward G 
Citation: Jiang L, etal., Hypertension. 2012 Nov;60(5):1192-9. doi: 10.1161/HYPERTENSIONAHA.112.196840. Epub 2012 Sep 24.
RGD ID: 13792498
Pubmed: PMID:23006733   (View Abstract at PubMed)
PMCID: PMC3487400   (View Article at PubMed Central)
DOI: DOI:10.1161/HYPERTENSIONAHA.112.196840   (Journal Full-text)

Age-associated central arterial wall stiffness is linked to extracellular matrix remodeling, including fibrosis and vascular calcification. Angiotensin II induces both matrix metalloproteinase 2 (MMP2) and calpain-1 expression and activity in the arterial wall. However, the role of calpain-1 in MMP2 activation and extracellular matrix remodeling remains unknown. Dual histo-immunolabeling demonstrates colocalization of calpain-1 and MMP2 within old rat vascular smooth muscle cells. Overexpression of calpain-1 induces MMP2 transcripts, protein levels, and activity, in part, by increasing the ratio of membrane type 1 MMPs to tissue inhibitor of metalloproteinases 2. These effects of calpain-1 overexpression-induced MMP2 activation are linked to increased collagen I and III production and vascular calcification. In addition, overexpression of calpain-1 also induces transforming growth factor-ß1/Smad signaling, elastin degradation, alkaline phosphatase activation, and total calcium content but reduces the expression of calcification inhibitors, osteopontin, and osteonectin, in cultured vascular smooth muscle cells in vitro and in carotid artery rings ex vivo. Furthermore, both calpain-1 and collagen II increase with aging within human aortic intima. Interestingly, in aged human aortic wall, both calpain-1 and collagen II are highly expressed in artherosclerotic plaque areas compared with grossly normal areas. Cross-talk of 2 proteases, calpain-1 and MMP2, leads to secretion of active MMP2, which modulates extracellular matrix remodeling via enhancing collagen production and facilitating vascular calcification. These results establish calpain-1 as a novel molecular candidate to retard age-associated extracellular matrix remodeling and its attendant risk for hypertension and atherosclerosis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
aortic atherosclerosis  ISOCapn1 (Rattus norvegicus)13792498; 13792498protein:increased activity:aortaRGD 
aortic atherosclerosis  IEP 13792498protein:increased activity:aortaRGD 

Objects Annotated

Genes (Rattus norvegicus)
Capn1  (calpain 1)

Genes (Mus musculus)
Capn1  (calpain 1)

Genes (Homo sapiens)
CAPN1  (calpain 1)


Additional Information