Significance of Impaired Serum Gelatinases Activities in Metabolic Syndrome


Affiliations

  • King George’s Medical University, Departments of Pharmacology and Therapeutics, Lucknow, Uttar Pradesh, India
  • King Khalid University Hospital, Department of Medical Education and Research, Riyadh, Saudi Arabia
  • King George’s Medical University, Internal Medicine, Lucknow, Uttar Pradesh, India

Abstract

Introduction: A consortium of metabolic risk factors accelerate the onset of diabetes, heart disease, stroke, and certain cancers. Proteolytic enzymes like matrix metalloproteinases (MMP) are regulated by a group of endogenous proteins called tissue inhibitors of metalloproteinases (TIMP). These TIMPs binds to active and alternate sites of activated MMPs and facilitate regulation. Impaired expression of MMPs may have a significant contribution in the pathogenesis of many tissues-destructive processes like tumor progression and cardiovascular and metabolic disorders. Materials and Methods: This case control study lays stress on the possible role of impaired levels of circulating MMP‑2 and 9 in metabolic syndrome (MetS). The age, sex‑matched 388 subjects with 190 newly diagnosed patients, and 198 healthy controls were recruited. To screen the patients with MetS, biochemical analysis of patients for impaired glucose level, hypertension, body mass index (BMI), and lipid profile was performed. The circulating level of MMP‑2 and ‑9 in serum was analyzed by enzyme‑linked immunosorbent assay (ELISA) in all patients and control. Results: All metabolic risk factors were statistically significant (P < 0.01) in patients against control group. The serum MMP‑2 and ‑9 level was significantly higher (P < 0.001) in patients having MetS as compared with control group. Conclusions: Similar trend was observed in gender wise analysis of serum MMP level. Higher MMP level alteration observed in male patients as compared with female patients.

Keywords

Insulin resistance, metabolic syndrome, matrix metalloproteinases‑2, matrix metalloproteinases‑9

Full Text:

References

Woessner JF. The matrix metalloproteinase family. In: Parks WC, Mecham RP, editors. Matrix Metalloproteinases. San Diego: Academic Press; 1998. p. 1‑14.

Derosa G, D’Angelo A, Scalise F, Avanzini MA, Tinelli C, Peros E, et al. Comparison between metalloproteinases‑2 and ‑9 in healthy subjects, diabetics, and subjects with acute coronary syndrome. Heart Vessels 2007;22:361‑70.

Liu P, Sun M, Sader S. Matrix metalloproteinases in cardiovascular disease. Can J Cardiol 2006;22:25‑30B.

Amalinei C, Caruntu ID, Balan RA. Biology of metalloproteinases. Rom J Morphol Embryol 2007;48:323‑34.

Bourbolia D, Stetler‑Stevenson WG. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs): Positive and negative regulators in tumor cell adhesion. Semin Cancer Biol 2010;20:161‑8.

Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C.American Heart Association, National Heart, Lung, and Blood Institute. Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association Conference on scientific issues related to definition.

Circulation 2004;109:433‑8.

Deepa M, Farooq S, Datta M, Deepa R, Mohan V. Prevalence of metabolic syndrome using WHO, ATPIII and IDF definitions in Asian Indians: The Chennai Urban Rural Epidemiology Study (CURES‑34). Diabetes Metab Res Rev 2007;23:127‑34.

ICMR Task force project on collaborative study of coronary heart disease; National cardiovascular disease Database sticker no: SE/04/233208:15- 18.

Kamble P, Deshmukh PR, Garg N. Metabolic syndrome in adult population of rural Wardha, central India. Indian J Med Res 2010;132:701‑5.

Gonçalves FM, Jacob‑Ferreira AL, Gomes VA, Casella‑Filho A, Chagas AC, Marcaccini AM, et al. Increased circulating levels of matrix metallo‑proteinase (MMP)‑8, MMP‑9, and pro‑inflammatory markers in patients with metabolic syndrome. Clin Chim Acta 2009;403:173‑7.

Hopps E, Lo Presti R, Montana M, Noto D, Averna MR, Caimi G. Gelatinases and their tissue inhibitors in a group of subjects with metabolic syndrome. J Investig Med 2013;61:978‑83.

Derosa G, Ferrari I, D’Angelo A, Tinelli C, Salvadeo SA, Ciccarelli L, et al. Matrix metalloproteinase‑2 and ‑9 levels in obese patients. Endothelium 2008;15:219‑24.

Derosa G, Maffioli P, D’Angelo A, Salvadeo SA, Ferrari I, Fogari E, et al. Evaluation of metalloproteinase 2 and 9 levels and their inhibitors in combined dyslipidemia. Clin Invest Med 2009;32:E124‑32.

Derosa G, D’Angelo A, Tinelli C, Devangelio E, Consoli A, Miccoli R, et al. Evaluation of metalloproteinase 2 and 9 levels and their inhibitors in diabetic and healthy subjects. Diabetes Metab 2007;33:129‑34.

Mieczkowska J, Mosiewicz J, Barud W, Kwaśniewski W. Changes in the activity of connective tissue matrix enzymes in the metabolic syndrome. Arch Med Sci 2011;7:634‑41.

Derosa G, D’Angelo A, Ciccarelli L, Piccinni MN, Pricolo F, Salvadeo S, et al. Matrix metalloproteinase‑2, ‑9, and tissue inhibitor of metalloproteinase‑1 in patients with hypertension. Endothelium 2006;13:227‑31.

Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486‑97.

Berg G, Miksztowicz V, Schreier L. Metalloproteinases in metabolic syndrome. Clin Chim Acta 2011;412:1731‑9.

Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res 2010;107:1058‑70.

Federici M, Menghini R, Mauriello A, Hribal ML, Ferrelli F, Lauro D, et al. Insulindependent activation of endothelial nitric oxide synthase is impaired by O‑linked glycosylation modification of signalling proteins in human coronary endothelial cells. Circulation 2002;106:466‑72.

Cardellini M, Menghini R, Martelli E, Casagrande V, Marino A, Rizza S, et al. TIMP3 is reduced in atherosclerotic plaques from subjects with type 2 diabetes and increased by SirT1. Diabetes 2009;58:2396‑401.

Death AK, Fisher EJ, McGrath KC, Yue DK. High glucose alters matrix metallo‑proteinase expression in two key vascular cells: Potential impact on atherosclerosis in diabetes. Atherosclerosis 2003;168:263‑9.

Kosmala W, Plaksej R , Przewlocka ‑ Kosmala M , Kuliczkowska‑Plaksej J, Bednarek Tupikowska G, Mazurek W. Matrix metalloproteinases 2 and 9 and their tissue inhibitors 1 and 2 in premenopausal obese women: Relationship to cardiac function. Int J Obes (Lond) 2008;32:763‑71.

Głowińska‑Olszewska B, Urban M. Elevated matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in obese children and adolescents. Metabolism 2007;56:799‑805.

Unal R, Yao‑Borengasser A, Varma V, Rasouli N, Labbate C, Kern PA, et al. Matrix metalloproteinase‑9 is increased in obese subjects and decreases in response to pioglitazone. J Clin Endocrinol Metab 2010;95:2993‑3001.

Zhang SD, Yang L, Yu GL, Sun M, Zhou HY. Quantitative ultrasonic integrated backscatter of the intima–media complex, serum level of matrix metalloprotease‑9 and simvastatin in hyperlipemia patients. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2008;33:160‑4.

Jormsjo S, Whatling C, Walter DH, Zeiher AM, Hamsten A, Eriksson P. Allele‑specific regulation of matrix metalloproteinase‑7 promoter activity is associated with coronary artery luminal dimensions among hypercholesterolemic patients. Arterioscler Thromb Vasc Biol 2001;21:1834‑9.

Koh KK, Ahn JY, Jin DK, Han SH, Kim HS, Choi IS, et al. Comparative effects of statin and fibrate on nitric oxide bioactivity and matrix metalloproteinase in hyperlipidemia. Int J Cardiol 2004;97:239‑44.

Cicero AF, Derosa G, Manca M, Bove M, Borghi C, Gaddi AV.Vascular remodeling and prothromboticmarkers in subjects affected by familial combined hyperlipidemia and/or metabolic syndrome in primary prevention for cardiovascular disease. Endothelium 2007;14:193‑8.

Yadav SS, Mandal RK, Singh MK, Usman K, Khattri S. Genetic Variants of Matrix Metalloproteinase (MMP2) Gene Influence Metabolic Syndrome Susceptibility. Genet Test Mol Biomarkers 2013.

Miksztowicz V, Muzzio ML, Royer M, Prada M, Wikinski R, Schreier L, et al. Increased plasma activity of metallo‑proteinase 2 in women with metabolic syndrome. Metabolism 2008;57:1493‑6.

Gummesson A, Hagg D, Olson FJ, Hulthe J, Carlsson LM, Fagerberg B. Adipose tissue is not an important source for matrix metalloproteinase‑9 in the circulation. Scand J Clin Lab Invest 2009;69:636‑42.

Chu MC, Cushman M, Solomon R, Lobo RA. Metabolic syndrome in postmenopausal women: The influence of oral or transdermal estradiol on inflammation and coagulation markers. Am J Obstet Gynecol 2008;199:526.e1‑7.

Fanjul‑Fernández M, Folgueras A, Cabrera S, López‑Otín C. Matrix metalloproteinases: Evolution, gene regulation and functional analysis in mouse models. Biochim Biophys Acta 2010;1803:3‑19.


Refbacks

  • There are currently no refbacks.