Central pulse pressure and variability in matrix metalloproteinases genes and their inhibitors in patients with ischemic heart disease.

Matrix metalloproteinases (MMPs) as well as their inhibitors (TIMPs) play a crucial role in controlling extracellular matrix turnover and have recently been associated with atherosclerosis, myocardial and vascular injury. Moreover, the genetic variability of MMP genes has been suggested to play an important role in vascular remodeling and age-related arterial stiffening. This study aims to describe associations of 14 selected polymorphisms in genes for MMPs and TIMPs with selected cardiovascular parameters (including central pulse pressure), clinical conditions and drug treatment profiles in 411 stable ischemic patients with preserved systolic function of the left ventricle. The genotyping of 14 single-nucleotide polymorphisms in 8 genes was carried out either using 5´ exonuclease (TaqMan®) reagents or by restriction analysis. Numerous associations of the investigated polymorphisms with systolic and diastolic blood pressure, maximum left ventricular end diastolic pressure and ejection fraction were observed. While some of the observed effects were found to be age-dependent, associations with clinical conditions (hypertension, diabetes mellitus, angina pectoris) were only observed in women and associations with four groups of drugs (statins, nitrates, calcium channel blockers, anti-aggregation drugs) were only observed in men. The results of this study indicate that the genetic variability of MMPs and TIMPs is an important factor which influences cardiovascular functions and may have important consequences for individual therapy customization in the future.