The association between serum metalloproteinase concentration, obesity, and hormone levels in reproductive-aged women
Abstract
Introduction: Increased levels and activity of some matrix metalloproteinases (MMPs) are described in obesity-related vascular diseases. Factors that influence MMP blood concentration are still being investigated. This research aims to evaluate the concentration of most types of MMPs: collagenases (MMP-1, -3, -8, -13), matrilysin (MMP-7), gelatinase (MMP-9), and metalloelastase (MMP-12) in serum of women in reproductive age in relation with their body mass index (BMI), age, oestradiol, and progesterone concentrations. Material and methods: Blood samples were taken from 54 healthy reproductive-aged women with normal menstrual cycles. The weight and height of all women were measured, and body mass index (BMI) was calculated. Concentration of MMP-1, -3, -7, -8, -9, -12, and MMP-13 was evaluated using a Procarta Immunoassay Kit. Serum concentrations of oestradiol and progesterone were evaluated by immunochemiluminescence (32 in the proliferative and 20 in the secretory phase of menstrual cycle). The results of the study were statistically calculated using Pearson, Spearman, and Kruskal-Wallis tests. Results: Positive correlation between MMP-7, -8, -9, -12, and -13 levels and BMI was demonstrated. Significantly higher concentrations of MMPs were found especially in obese women compared to women with normal BMI. In healthy, regularly menstruating premenopausal women, MMP levels did not correlate with oestradiol and progesterone concentrations. Conclusions: The results suggest that body mass can influence MMP serum concentration in women with regular menstrual cycles.
Keywords: MMPobesitycardiovascular riskoestradiolprogesterone
References
- Van Gaal LF, Mertens IL, De Block CE. Mechanisms linking obesity with cardiovascular disease. Nature. 2006; 444(7121): 875–880.
- Kujawska-Łuczak M, Suliburska J, Markuszewski L, et al. The effect of L-arginine and ascorbic acid on the visceral fat and the concentrations of metalloproteinases 2 and 9 in high-fat-diet rats. Endokrynol Pol. 2015; 66(6): 526–532.
- Van Lint P, Libert C. Chemokine and cytokine processing by matrix metalloproteinases and its effect on leukocyte migration and inflammation. J Leukoc Biol. 2007; 82(6): 1375–1381.
- Nagase H, Visse R, Murphy G. Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res. 2006; 69(3): 562–573.
- Sikora-Szubert A, Kowalska-Koprek U, Karowicz-Bilinska A. [The analysis of selected biochemical parameters concentration in pregnant women with idiopathic edema of the lower limbs--preliminary report]. Ginekol Pol. 2012; 83(9): 660–664.
- Wu YW, Kao HL, Chen MF, et al. Characterization of plaques using 18F-FDG PET/CT in patients with carotid atherosclerosis and correlation with matrix metalloproteinase-1. J Nucl Med. 2007; 48(2): 227–233.
- Newby AC. Metalloproteinase expression in monocytes and macrophages and its relationship to atherosclerotic plaque instability. Arterioscler Thromb Vasc Biol. 2008; 28(12): 2108–2114.
- Lehrke M, Greif M, Broedl UC, et al. MMP-1 serum levels predict coronary atherosclerosis in humans. Cardiovasc Diabetol. 2009; 8: 50.
- Andrade VL, Petruceli E, Belo VA, et al. Evaluation of plasmatic MMP-8, MMP-9, TIMP-1 and MPO levels in obese and lean women. Clin Biochem. 2012; 45(6): 412–415.
- Bouloumié A, Sengenès C, Portolan G, et al. Adipocyte produces matrix metalloproteinases 2 and 9: involvement in adipose differentiation. Diabetes. 2001; 50(9): 2080–2086.
- Taskiran D, Evren V. Estradiol protects adipose tissue-derived stem cells against H(2)O(2)-induced toxicity. J Biochem Mol Toxicol. 2012; 26(8): 301–307.
- Emaus A, Espetvedt S, Veierød MB, et al. 17-beta-estradiol in relation to age at menarche and adult obesity in premenopausal women. Hum Reprod. 2008; 23(4): 919–927.
- Furcron AE, Romero R, Plazyo O, et al. Vaginal progesterone, but not 17α-hydroxyprogesterone caproate, has antiinflammatory effects at the murine maternal-fetal interface. Am J Obstet Gynecol. 2015; 213(6): 846.e1–846.e19.
- Martínez A, Oh HR, Unsworth EJ, et al. Matrix metalloproteinase-2 cleavage of adrenomedullin produces a vasoconstrictor out of a vasodilator. Biochem J. 2004; 383(Pt. 3): 413–418.
- Cavusoglu E, Marmur J, Hegde S, et al. Relation of baseline plasma MMP-1 levels to long-term all-cause mortality in patients with known or suspected coronary artery disease referred for coronary angiography. Atherosclerosis. 2015; 239(1): 268–275.
- Austin KM, Covic L, Kuliopulos A. Matrix metalloproteases and PAR1 activation. Blood. 2013; 121(3): 431–439.
- Lijnen HR, Silence J, Van Hoef B, et al. Stromelysin-1 (MMP-3)-independent gelatinase expression and activation in mice. Blood. 1998; 91(6): 2045–2053.
- Tziakas DN, Chalikias GK, Papaioakeim M, et al. Comparison of levels of matrix metalloproteinase-2 and -3 in patients with ischemic cardiomyopathy versus nonischemic cardiomyopathy. Am J Cardiol. 2005; 96(10): 1449–1451.
- Kwon S, Weiden MD, Echevarria GC, et al. Early elevation of serum MMP-3 and MMP-12 predicts protection from World Trade Center-lung injury in New York City Firefighters: a nested case-control study. PLoS One. 2013; 8(10): e76099.
- Catrina AI, Lampa J, Ernestam S, et al. Anti-tumour necrosis factor (TNF)-alpha therapy (etanercept) down-regulates serum matrix metalloproteinase (MMP)-3 and MMP-1 in rheumatoid arthritis. Rheumatology (Oxford). 2002; 41(5): 484–489.
- Park JiY, Park JH, Jang W, et al. Apolipoprotein A-IV is a novel substrate for matrix metalloproteinases. J Biochem. 2012; 151(3): 291–298.
- Väyrynen JP, Vornanen J, Tervahartiala T, et al. Serum MMP-8 levels increase in colorectal cancer and correlate with disease course and inflammatory properties of primary tumors. Int J Cancer. 2012; 131(4): E463–E474.
- Aquilante CL, Beitelshees AL, Zineh I. Correlates of serum matrix metalloproteinase-8 (MMP-8) concentrations in nondiabetic subjects without cardiovascular disease. Clin Chim Acta. 2007; 379(1-2): 48–52.
- Kosmala W, Plaksej R, Przewlocka-Kosmala M, et al. 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(5): 763–771.
- Garvin P, Nilsson L, Carstensen J, et al. Circulating matrix metalloproteinase-9 is associated with cardiovascular risk factors in a middle-aged normal population. PLoS One. 2008; 3(3): e1774.
- Kaspiris A, Khaldi L, Chronopoulos E, et al. Macrophage-specific metalloelastase (MMP-12) immunoexpression in the osteochondral unit in osteoarthritis correlates with BMI and disease severity. Pathophysiology. 2015; 22(3): 143–151.
- Chavey C, Mari B, Monthouel MN, et al. Matrix metalloproteinases are differentially expressed in adipose tissue during obesity and modulate adipocyte differentiation. J Biol Chem. 2003; 278(14): 11888–11896.
- Halpert I, Sires UI, Roby JD, et al. Matrilysin is expressed by lipid-laden macrophages at sites of potential rupture in atherosclerotic lesions and localizes to areas of versican deposition, a proteoglycan substrate for the enzyme. Proc Natl Acad Sci U S A. 1996; 93(18): 9748–9753.
- Howes JM, Bihan D, Slatter DA, et al. The recognition of collagen and triple-helical toolkit peptides by MMP-13: sequence specificity for binding and cleavage. J Biol Chem. 2014; 289(35): 24091–24101.
- Shih CLM, Ajuwon KM. Inhibition of MMP-13 prevents diet-induced obesity in mice and suppresses adipogenesis in 3T3-L1 preadipocytes. Mol Biol Rep. 2015; 42(7): 1225–1232.
- Suzuki H, Kusuyama T, Sato R, et al. Elevation of matrix metalloproteinases and interleukin-6 in the culprit coronary artery of myocardial infarction. Eur J Clin Invest. 2008; 38(3): 166–173.
- Meides A, Gutschalk CM, Devel L, et al. Effects of selective MMP-13 inhibition in squamous cell carcinoma depend on estrogen. Int J Cancer. 2014; 135(12): 2749–2759.
