Role of Gelatinases MMP-2 and MMP-9 in Healthy and Complicated Pregnancy and Their Future Potential as Preeclampsia Biomarkers.

Gelatinases (matrix metalloproteinase-2 and -9) are enzymes from the matrix metalloproteinases (MMPs) family, which are associated with collagen degradation. MMP-2 is capable of cleaving gelatine, types I and IV collagens, while MMP-9 is incapable of direct proteolysis of collagen I and digests collagen type IV. MMP-2 and -9 are both important regulators of vascular and uterine remodeling in a healthy pregnancy. Alterations in the collagen structure of the uterus and spiral arteries are observed in women with hypertensive disorders of pregnancy. Dysregulation of MMP-2 and MMP-9 has been implicated in abnormal vasodilation, placentation, and uterine expansion in preeclampsia. Early preeclampsia detection is paramount for risk stratification and prevention of further complications. Understanding the role of MMP-2 and-9 in uteroplacental and vascular remodeling could help design new approaches for prediction and management of preeclampsia. This review presents a general survey of MMP-2 and MMP-9 faulty regulation and impaired collagen types I and IV turnover in complicated pregnancies. Their potential role as circulating markers for diagnosis, prognosis, and monitoring of preeclampsia development is discussed as well.

Temporal changes in integrin-mediated cardiomyocyte adhesion secondary to chronic cardiac volume overload in rats.

Previous studies have established integrins as cell surface receptors that mediate cardiomyocyte-extracellular matrix (ECM) attachments. This study sought to determine the contributions of the myocardial ß1- and ß3-integrin subunits to ventricular dilatation and coronary flow regulation using a blood-perfused isolated heart preparation. Furthermore, cardiomyocyte adhesion to collagen types I and IV, fibronectin, and laminin with and without a ß1-integrin subunit neutralizing antibody was assessed during the course of remodeling secondary to a sustained cardiac volume overload, including the onset of heart failure. Isolated cardiomyocytes were obtained during the initial, compensated, and decompensated phases of remodeling resulting from an aortocaval fistula created in 8-wk-old male Sprague-Dawley rats. Blocking the ß1-integrin subunit in isolated normal hearts produced ventricular dilatation, whereas this was not the case when the ß3-subunit was blocked. Substantial reductions in cardiomyocyte adhesion coincided with the previously documented development of ventricular dilatation and decreased contractility postfistula, with the ß1-integrin contribution to adhesion ranging from 28% to 73% over the course of remodeling being essentially substrate independent. In contrast, both integrin subunits were found to be involved in regulating coronary vascular resistance. It is concluded that marked reductions in integrin-mediated cardiomyocyte adhesion to the ECM play a significant role in the progression of adverse myocardial remodeling that leads to heart failure. Furthermore, although both the ß1- and ß3-integrin subunits were involved in regulating coronary vascular resistance, only inhibition of ß1-integrin-mediated adhesion resulted in ventricular dilatation of the normal heart.