Title:Matrix Metalloproteinases as Drug Targets in Acute Pulmonary Embolism
VOLUME: 14 ISSUE: 3
Author(s):Evandro M. Neto-Neves, Tamas Kiss, Diana Muhl and Jose E. Tanus-Santos
Affiliation:Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeirao Preto, SP, Brazil.
Keywords:Acute pulmonary thromboembolism, matrix metalloproteinases, pulmonary circulation, pulmonary embolism, pulmonary
hypertension, therapy, hrombolysis, Brain Natriuretic Peptide (BNP), Cardiac Troponins, Fatty Acid Binding Protein
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.
