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Mol Med. 2016 Oct;22:487-496. doi: 10.2119/molmed.2016.00068. Epub 2016 Jun 30.

Identification of matrix metalloproteinase-12 as a candidate molecule for prevention and treatment of cardiometabolic disease.

Author information

1
Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
2
Center for Medical Statistics, Informatics, and Intelligent Systems, Section for Medical Statistics, Medical University of Vienna, Austria.
3
Core Facility Genomics, Core Facilities, Medical University of Vienna, Vienna, Austria.
4
Institute for Computational Health Sciences. University of California, San Francisco, EEUU.
5
AFFiRiS GmbH, Vienna, Austria.
6
Department of Pediatrics and Adolescent Medicine, Clinical Division of Pediatric Pulmonology, Allergology and Endocrinology, Medical University of Vienna.

Abstract

Obesity is strongly associated with metabolic syndrome, a combination of risk factors that predispose to the development of the cardiometabolic diseases: atherosclerotic cardiovascular disease and type 2 diabetes mellitus. Prevention of metabolic syndrome requires novel interventions to address this health challenge. The objective of this study was the identification of candidate molecules for the prevention and treatment of insulin resistance and atherosclerosis, conditions that underlie type 2 diabetes mellitus and cardiovascular disease, respectively. We used an unbiased bioinformatics approach to identify molecules that are upregulated in both conditions by combining murine and human data from a microarray experiment and meta-analyses. We obtained a pool of eight genes that were upregulated in all the databases analysed. This included well known and novel molecules involved in the pathophysiology of type 2 diabetes mellitus and cardiovascular disease. Notably, matrix metalloproteinase 12 (MMP12) was highly ranked in all analyses and was therefore chosen for further investigation. Analyses of visceral and subcutaneous white adipose tissue from obese compared to lean mice and humans convincingly confirmed the up-regulation of MMP12 in obesity at mRNA, protein and activity levels. In conclusion, using this unbiased approach an interesting pool of candidate molecules was identified, all of which have potential as targets in the treatment and prevention of cardiometabolic diseases.

KEYWORDS:

Cardiovascular diseases; Diabetes Mellitus, Type 2; Insulin Resistance; Meta-Analysis; Metabolic Syndrome; Microarray Analysis

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