Matrix metalloproteinases (MMPs) are a family of endopeptidases that degrade the components of the extracellular matrix (ECM) such as collagen, and thus contribute to the remodelling and the physiological homeostasis of the ECM and its blood supply. The activities of these enzymes are regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs), and it has been suggested that a balance between MMPs and TIMPs plays an important role in vascular remodelling, angiogenesis and vasodilatation in a number of physiological situations. It follows that, regarding a relationship between MMPs and TIMPs, an imbalance between these molecules may lead to pathology in a wide range of conditions, including hypertension, cancer and pulmonary disease, and in the pathophysiology of reproduction. Indeed, regarding the latter, abnormalities in the maternal peripheral vasculature have been proposed as being (partly) responsible for the effects of hypertension on pregnancy and the development of complications including pre-eclampsia and eclampsia. However, the associations between MMPs, TIMPs and disease may be simply of association, not of pathology. This brief review explores current literature on the role of abnormalities of the ECM in general, focusing on the pathogenesis of hypertension and its complications during pregnancy as a model of disordered angiogenesis and remodelling.
We have not found any convincing excess of congenital anomalies in women taking angiotensin-blocking drugs in early pregnancy. However, this does not exclude the possibility that ACE-I or ARB use in pregnancy might lead to adverse obstetrical outcomes. Until this matter is settled, we support recommendations that these drugs should not be used in pregnancy or in women who are likely to become pregnant.
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