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Circulating and adipose tissue matrix metalloproteinases in cardiometabolic risk environments: pathophysiological
Abstract:
Matrix metalloproteinases (MMPs) play an important role during physiological tissue remodeling in embryonic development and angiogenesis, as well as in pathophysiological conditions such as obesity and development and vulnerability of atherosclerotic plaque. Moreover, MMP circulating levels have emerged as potential biomarkers of cardiovascular disease. MMP expression and activity are regulated by different factors such as insulin resistance and obesity. Expanded fat tissue has been demonstrated to be an active organ, where MMPs also exert a role in adipogenesis, angiogenesis, and proliferation of extracellular matrix (ECM). However, the lack of association between adipose tissue and plasma levels of some MMPs, specifically MMP-2 and MMP-9, suggests that this tissue is not a major contributor to circulating gelatinases. MMPs are also co-expressed or co-repressed in response to inflammatory adipocytokines, like adiponectin and leptin. Adiponectin may also play a protective role in plaque rupture through selectively increasing the tissue inhibitor of metalloproteinase (TIMP) expression. Leptin induces the expression of MMP-2 activators as well as the expression of MMP-2, MMP-9, and TIMP-1 in different human cells. Furthermore, sex hormones also participate in MMP regulation. In postmenopausal women, hormone replacement therapy produces an increase in MMP activity, leading to a breakdown in ECM homeostasis and accelerated progression of vascular pathologies. Besides, in men, an inverse relationship between testosterone levels and MMP-2 activity has been described. It is still necessary to go forward in the study of MMPs in different metabolic situations to corroborate their role as vulnerable plaque biomarkers.
Insights
Matrix metalloproteinases (MMPs) are key in tissue remodeling and cardiovascular disease. Their levels are influenced by obesity, hormones, and adipokines, impacting atherosclerotic plaque vulnerability.
Area of Science:
- Biochemistry
- Molecular Biology
- Cardiovascular Research
Background:
- Matrix metalloproteinases (MMPs) are crucial for physiological tissue remodeling, embryonic development, and angiogenesis.
- Dysregulated MMPs are implicated in pathophysiological conditions like obesity and atherosclerotic plaque development and vulnerability.
- Circulating MMP levels are emerging as potential biomarkers for cardiovascular disease.
Purpose of the Study:
- To explore the role of MMPs in metabolic conditions and their association with atherosclerotic plaque vulnerability.
- To investigate the regulation of MMPs by factors such as obesity, insulin resistance, adipocytokines, and sex hormones.
- To clarify the contribution of adipose tissue to circulating MMP levels.
Main Methods:
- Review and synthesis of existing literature on MMPs in metabolic and cardiovascular contexts.
- Analysis of the interplay between MMPs, adipokines (adiponectin, leptin), sex hormones, and extracellular matrix (ECM) homeostasis.
- Examination of MMP expression and activity in relation to obesity, insulin resistance, and atherosclerotic plaque characteristics.
Main Results:
- Adipose tissue plays a role in adipogenesis and angiogenesis but may not be a major source of circulating MMP-2 and MMP-9.
- MMPs are co-regulated with adipokines like adiponectin and leptin, influencing plaque stability.
- Sex hormones modulate MMP activity; hormone replacement therapy in postmenopausal women increases MMP activity, while testosterone inversely correlates with MMP-2 activity in men.
Conclusions:
- MMPs are significantly regulated by metabolic factors and hormones, influencing cardiovascular disease progression.
- Adiponectin and leptin modulate MMPs, with adiponectin potentially offering a protective role against plaque rupture.
- Further research into MMPs in various metabolic states is needed to confirm their utility as biomarkers for vulnerable atherosclerotic plaques.
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