title: Matrix metalloproteinases as drug targets in acute pulmonary embolism.
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.
authors: Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeirao Preto, SP, Brazil.
authors: Evandro M
authors: EM
authors: Neto-Neves
authors: Tamas
authors: T
authors: Kiss
authors: Diana
authors: D
authors: Muhl
authors: Jose E
authors: JE
authors: Tanus-Santos
mesh_terms: D000208:Acute Disease; D000818:Animals; D015415:Biomarkers; D050556:Fatty Acid-Binding Proteins / Q000097:blood; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors / Q000627:therapeutic use*; D020782:Matrix Metalloproteinases / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011655:Pulmonary Embolism / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology; D014336:Troponin / Q000097:blood
chemical_list: D015415:Biomarkers; D050556:Fatty Acid-Binding Proteins; D005338:Fibrin Fibrinogen Degradation Products; D061965:Matrix Metalloproteinase Inhibitors; D014336:Troponin; C036309:fibrin fragment D; D020097:Natriuretic Peptide, Brain; D020782:Matrix Metalloproteinases