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Current Drug Targets
ISSN (Print): 1389-4501
ISSN (Online): 1873-5592
VOLUME: 14
ISSUE: 3
DOI: 10.2174/1389450111314030006      Price:  $58









Matrix Metalloproteinases as Drug Targets in Acute Pulmonary Embolism

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Author(s): Evandro M. Neto-Neves, Tamas Kiss, Diana Muhl and Jose E. Tanus-Santos
Pages 344-352 (9)
Abstract:
Acute pulmonary embolism is a critical condition associated with increased mortality. Lung embolization causes acute pulmonary hypertension and right ventricle afterload. Global heart ischemia supervenes and may lead to severe shock and death. In this article, we reviewed current literature supporting the idea that abnormal matrix metalloproteinase (MMP) activity contributes to acute pulmonary embolism-induced hemodynamic changes. While low MMP levels are usually found in normal lung tissues, it is well known that inflammation and lung injury increase MMP expression and activity. This is probably due to recruitment and migration of inflammatory cells from the circulation to lung tissues. In addition, recent studies have shown increased MMP levels and activity in the right ventricle from animals with acute pulmonary embolism. Such increases in proteolytic activity were associated with increased cardiac troponin I in serum, suggesting a possible role for MMPs in cardiomyocyte injury during acute pulmonary embolism. These alterations have justified the use of doxycycline as an MMP inhibitor in acute pulmonary embolism. We review current evidence indicating that MMPs are targets in this critical condition. MMP inhibition apparently exerts antihypertensive effects and protects against cardiomyocyte injury caused by acute pulmonary embolism.
Keywords:
Acute pulmonary thromboembolism, matrix metalloproteinases, pulmonary circulation, pulmonary embolism, pulmonary hypertension, therapy, hrombolysis, Brain Natriuretic Peptide (BNP), Cardiac Troponins, Fatty Acid Binding Protein
Affiliation:
Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeirao Preto, SP, Brazil.