Identification of Matrix Metalloproteinase-12 as a Candidate Molecule for Prevention and Treatment of Cardiometabolic Disease
Identification of Matrix Metalloproteinase-12 as a Candidate Molecule for Prevention and Treatment of Cardiometabolic Disease
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DOI：
10.2119/molmed.2016.00068
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发表时间：
2016-01-01
影响因子：
5.7
通讯作者：
Stulnig, Thomas M.
中科院分区：
文献类型：
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作者：
Amor, Melina;Moreno-Viedma, Veronica;Stulnig, Thomas M.
肥胖与代谢综合征密切相关，代谢综合征是一组易患心脏代谢性疾病的危险因素的组合：动脉粥样硬化性心血管疾病和2型糖尿病。预防代谢综合征需要新的干预措施来应对这一健康挑战。这项研究的目的是确定预防和治疗胰岛素抵抗和动脉粥样硬化的候选分子，这两种疾病分别是2型糖尿病和心血管疾病的基础。我们使用一种无偏见的生物信息学方法，通过结合来自微阵列实验和荟萃分析的鼠类和人类数据，识别在这两种情况下上调的分子。我们获得了一个在所有分析的数据库中上调的8个基因库。这包括与2型糖尿病和心血管疾病的病理生理学有关的众所周知的和新的分子。值得注意的是，基质金属蛋白酶12(MMP12)在所有分析中排名很高，因此被选为进一步研究的对象。对肥胖者内脏和皮下白色脂肪组织的分析，与瘦小鼠和人类相比，令人信服地证实了MMP12在mRNA、蛋白质和活动水平上的肥胖上调。总之，通过使用这种无偏见的方法，确定了一个有趣的候选分子池，所有这些分子都有可能成为治疗和预防心脏代谢性疾病的靶点。
Obesity is strongly associated with metabolic syndrome, a combination of risk factors that predisposes to 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 to identify 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 8 genes that were upregulated in all the databases analyzed. 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 with lean mice and humans convincingly confirmed the upregulation of MMP12 in obesity at the mRNA, protein and activity levels. In conclusion, by 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.