Imbalanced matrix metalloproteinases in cardiovascular complications of end-stage kidney disease: a potential pharmacological target.
End-stage kidney disease (ESKD) is a major health problem associated with very high morbidity and mortality secondary to cardiovascular complications, especially in ESKD patients on dialysis. Therefore, exploring key mechanisms underlying cardiovascular alterations associated with ESKD may offer reasonable pharmacological targets that may benefit these patients. Imbalanced matrix metalloproteinases (MMP) activities have been implicated in many cardiovascular diseases, and growing evidence now indicates that excessive MMP activities contribute to cardiovascular complications in ESKD patients. However, there is no study on the effects of MMP inhibitors (MMPIs) in such patients. MMPIs may prevent against the vascular and cardiac changes associated with ESKD. In this MiniReview, we aimed at reviewing current evidence supporting the idea that pharmacological inhibition of imbalanced MMP activities in ESKD may decrease the morbidity and mortality associated with cardiovascular complications in ESKD patients. However, MMPs have variable effects during different phases of kidney disease, and therefore optimal timing for MMP inhibition during a disease process may vary significantly and is largely undetermined. While current research shows that MMPs play a role in the pathogenesis of the cardiovascular alterations found in ESKD patients, clinical studies are required to validate the idea of using MMPIs in ESKD.
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, São Paulo, Brazil.
Bernardo P
BP
Marson
Carlos E
CE
Poli de Figueiredo
Jose E
JE
Tanus-Santos
D050197:Atherosclerosis / Q000209:etiology / Q000503:physiopathology; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D004318:Doxycycline / Q000494:pharmacology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology*; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D058990:Molecular Targeted Therapy / Q000379:methods*; D006435:Renal Dialysis; D012307:Risk Factors; D013777:Tetrazoles / Q000494:pharmacology; D014511:Uremia / Q000209:etiology / Q000378:metabolism
D001562:Benzimidazoles; D001713:Biphenyl Compounds; D061965:Matrix Metalloproteinase Inhibitors; D013777:Tetrazoles; D020782:Matrix Metalloproteinases; D004318:Doxycycline; C081643:candesartan