Fetal hypoxia and programming of matrix metalloproteinases

Abstract

Fetal hypoxia adversely affects the brain and heart development, yet the mechanisms responsible remain elusive. Recent studies indicate an important role of the extracellular matrix in fetal development and tissue remodeling. The matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs) have been implicated in a variety of physiological and pathological processes in the cardiovascular and central nervous systems. This review summarizes current knowledge of the mechanisms by which fetal hypoxia induces the imbalance of MMPs, TIMPs and collagen expression patterns, resulting in growth restriction and aberrant tissue remodeling in the developing heart and brain. Collectively, this information could lead to the development of preventive diagnoses and therapeutic strategies in the fetal programming of cardiovascular and neurological disorders.

Matrix metalloproteinase 2 of grass carp Ctenopharyngodon idella (CiMMP2) is involved in the immune response against bacterial infection

“…Recent studies indicate that the timely breakdown of ECM is crucial for normal fetal development [2], and MMPs are among the most significant mediators of ECM turnover during development [66]. Zebrafish MMPs have also been reported to have important roles in the early stages of zebrafish development, including the critical stages of gastrulation [67].…”

Alteration in the expression of the renin-angiotensin system in the myocardium of mice conceived by in vitro fertilization†

“…Increased plasma levels of CTGF may be a marker of pulmonary arterial hypertension associated with congenital heart disease [63]. An abnormal expression of COL1 and COL3 in the embryonic period may affect the heart's structural development [25]. Sustained changes in the expression of COL1 and COL3 in adulthood would further increase the risk of cardiovascular diseases, such as hypertension, arrhythmia, and cardiac hypertrophy, and enhance the process of cardiovascular fibrosis and remodeling [26].…”

“…Excessive activation of AGTR1 results in increased expression levels of the extracellular matrix components, such as collagen 1 (COL1) and collagen 3 (COL3) [22], which are distributed in several layers of the heart wall to provide rigidity and elasticity [23]. During the embryonic period, abnormal expression of COL1 and COL3 can affect the normal development of the cardiovascular structures [24,25]. In adulthood, overstimulation of the RAS can contribute to the pathogenesis of a number of cardiovascular diseases, affecting the normal function of cardiovascular tissue cells and increasing the risk of hypertension, heart arrhythmias, and cardiac hypertrophy [26].…”

Developmental determinants of cardiac sensitivity to hypoxia

“…In addition to cardiomyocyte hypertrophy, alterations in components of the extracellular matrix (ECM), specifically interstitial collagens in the heart, are seen in cardiac remodeling caused by hypoxia. Meanwhile, the changes in matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) might be initiated to compensate for the accumulation and deposition of collagens; however, the interruption of the fine balance between MMPs and TIMPs after hypoxia might eventually decompensate and impair the fetal heart morphology and function (Tong and Zhang, 2011). Bae et al (2003) have observed that maternal chronic hypoxia (10.5% oxygen, 7 days) led to the expression of HIF1␣ and increased apoptotic cell death in fetal rat hearts.…”