Acute actions and novel targets of matrix metalloproteinases in the heart and vasculature

Abstract

Matrix metalloproteinases (MMPs) have been shown to play significant roles in a number of physiological as well as pathological processes. Best known to proteolyse components of the extracellular matrix, MMPs have recently been discovered to also target a growing list of proteins apart from these, both inside and outside the cell. MMPs have also been traditionally thought of as enzymes involved in chronic processes such as angiogenesis, remodelling and atherosclerosis on a days-week time-scale. However they are now understood to also act acutely in response to oxidative stress on a minutes time-scale on non-extracellular matrix substrates. This review focuses on the acute actions and both extracellular and intracellular targets of two prominent MMP family members, MMP-2 and -9, in cardiovascular diseases including ischaemia/reperfusion injury, inflammatory heart disease, septic shock and pre-eclampsia. Also discussed are various ways of regulating MMP activity, including post-translational mechanisms, the endogenous tissue inhibitors of metalloproteinases and pharmacological inhibitors. A comprehensive understanding of MMP biology is necessary for the development of novel pharmacological therapies to combat the impact of cardiovascular disease.

Activation of nicotinamide N-methyltrasferase and increased formation of 1-methylnicotinamide (MNA) in atherosclerosis

“…As such, the assessment of gelatinase activity provides a relatively easy and comprehensive marker of vascular inflammation in atherosclerotic vessels. This notion stays in line with the important role of MMP-2 and MMP-9 in the initiation and progression of high cholesterol-driven vascular inflammation and atherosclerosis [11].…”

Matrix metalloproteinase 9 expression: new regulatory elements

“…MMP-9 is considered one of the pharmacological targets in the treatment of glaucoma [15] and other diseases [19][20][21][22]. Thus, the knowledge of the mechanisms regulating MMP-9 is important for the understanding of the neuron survivaldeath pathways and for deciphering the glaucomatous alterations in the retina and optic nerve.…”

Circulating matrix metalloproteinases and their endogenous inhibitors in patients with erectile dysfunction

“…10 Recent studies have implicated matrix metalloproteinases (MMPs) as key players in the functional and structural cardiovascular alterations associated with hypertension [12][13][14][15] and with other cardiovascular diseases. 16,17 Although MMPs are widely known to degrade the components of the extracellular matrix, they also have many other roles that are now being widely studied, especially in the cardiovascular system. 17,18 However, although imbalanced MMPs activities may underlie the vascular alterations of many cardiovascular diseases, there is no study examining the hypothesis that patients with ED have imbalanced levels of MMPs.…”

“…16,17 Although MMPs are widely known to degrade the components of the extracellular matrix, they also have many other roles that are now being widely studied, especially in the cardiovascular system. 17,18 However, although imbalanced MMPs activities may underlie the vascular alterations of many cardiovascular diseases, there is no study examining the hypothesis that patients with ED have imbalanced levels of MMPs. In addition, while there is evidence showing increased MMPs levels in DM, 19 there is no study comparing MMPs levels in diabetic and nondiabetic patients with ED.…”