Matrix metalloproteinase-2 degrades the cytoskeletal protein α-actinin in peroxynitrite mediated myocardial injury

Recombinant Human Matrix Metalloproteinase‐2 Impairs Cardiovascular β‐Adrenergic Responses

“…However, recent studies are clearly showing that MMP-2 may have many other targets unrelated to the extracellular matrix, including intracellular substrates [11,12] and other mediators possibly affecting the vascular tone such as bigendothelin-1[13], calcitonin gene-related peptide [14] and adrenomedullin [15]. Importantly, activated MMP-2 has been shown to impair cardiac function possibly as a result of its activity targeting sarcomeric and cytoskeletal proteins such as troponin I, myosin light chain-1, a-actinin and titin [16][17][18][19][20].Recent studies indicate that MMPs, including MMP-2, are involved in proteolytic cleavage of b 1 -and b 2 -adrenoreceptors [21]. Rodrigues et al [22] demonstrated that the labelling density of the extracellular domain of b 2 -adrenergic receptor in aortic endothelial cells from Wistar rats was reduced after treatment with plasma of spontaneously hypertensive rats with increased MMPs levels, thus indicating cleavage of b 2 -adrenergic receptors.…”

“…However, recent studies are clearly showing that MMP-2 may have many other targets unrelated to the extracellular matrix, including intracellular substrates [11,12] and other mediators possibly affecting the vascular tone such as bigendothelin-1[13], calcitonin gene-related peptide [14] and adrenomedullin [15]. Importantly, activated MMP-2 has been shown to impair cardiac function possibly as a result of its activity targeting sarcomeric and cytoskeletal proteins such as troponin I, myosin light chain-1, a-actinin and titin [16][17][18][19][20].…”

Trials, tribulations and speculation! Report from the 7th Biennial Hatter Cardiovascular Institute Workshop

“…However, more recently, MMPs have been demonstrated to have intracellular targets -cytoskeletal [2,3], contractile [4,5] and potentially also in terms of cell survival and cell death pathways [6,7]. Robert Bell and Derek Yellon presented data demonstrating that not only does MMP inhibition at reperfusion attenuate infarction in both in-vitro and in-vivo preparations, but the protection observed is additional to that seen following targeted deletion of the cyclophillin-D component of the mPTP.…”

Peroxynitrite - matrix metalloproteinase and erythropoietin receptor signaling pathways in ischemic heart disease

“…A plausible explanation is that MMP-2 activation and release can be less sensitively detected in the serum than that of MMP-9. While MMP-9 is an abundant enzyme in different cells and tissues including macrophages and leukocytes, MMP-2 is an intracellular enzyme occurring mainly in contractile tissues that can be activated and released; for example, due to acute myocardial ischemia/reperfusion and infarction [18,[68][69][70][71]. However, our CAD patient population did not have severe ischemia at the time of tissue sampling.…”

“…Pharmacological Research 113 (2016) [62][63][64][65][66][67][68][69][70] Erythropoietin (EPO) has been shown to protect the heart against acute myocardial infarction in preclinical studies, however, EPO failed to reduce infarct size in clinical trials and showed significant safety problems. Here, we investigated cardioprotective effects of two selective non-erythropoietic EPO receptor ligand dimeric peptides (AF41676 and AF43136) lacking erythropoietic activity, EPO, and the prolonged half-life EPO analogue, darbepoetin in acute myocardial infarction (AMI) in rats.…”