Matrix metalloproteinase -12: A marker of preeclampsia?

INTRODUCTION: Enzymes, including matrix metalloproteinases (MMPs), play a significant role in trophoblast invasion - the cornerstone of preeclampsia pathogenesis. METHODS: This study aimed to explore the dynamics of the MMP-12 concentration in blood serum during the gestational period at determined weeks in preeclampsia and physiological pregnancy to compare the results with the expression of MMP-12 in placental tissue and reveal the MMP-12 predicting role in preeclampsia. RESULTS: Circulating serum MMP-12 was significantly decreased. The level of 0.5 ng/ml had high sensitivity and low false positivity at 11-13 weeks of pregnancy in women destined to develop pre-eclampsia in the case-control study. The dynamics curve of serum MMP-12 varied between study groups: a sharp decrease in MMP-12 concentration was found from the first trimester to the second trimester, followed by a slight increase in the third trimester of pregnancy in controls compared to the increase in concentration from the first trimester to the second trimester in pre-eclampsia. The absence of a significant difference in the concentration of MMP-12 in the II and III trimesters as well as no difference in the expression of MMP-12 protein in placental tissue in the third trimester indicates a decrease in its role after the end of placentation. DISCUSSION: To our knowledge, this is the first study to show the dynamics of serum MMP-12 concentration during the gestational period and indicates a significant role for MMP-12 in the initial stages of placentation. The data obtained may pave the way to new early prediction strategies for preeclampsia.

Keratosis pilaris and ulerythema ophryogenes associated with an 18p deletion caused by a Y/18 translocation.

We present a patient with partial monosomy of the short arm of chromosome 18 caused by de novo translocation t(Y;18) and a generalized form of keratosis pilaris (keratosis pilaris affecting the skin follicles of the trunk, limbs and face-ulerythema ophryogenes). Two-color FISH with centromere-specific Y and 18 DNA probes identified the derivative chromosome 18 as a dicentric with breakpoints in p11.2 on both involved chromosomes. The patient had another normal Y chromosome. This is a third report the presence of a chromosome 18p deletion (and first case of a translocation involving 18p and a sex chromosome) with this genodermatosis. Our data suggest that the short arm of chromosome 18 is a candidate region for a gene causing keratosis pilaris. Unmasking of a recessive mutation at the disease locus by deletion of the wild type allele could be the cause of the recessive genodermatosis.

The creatine kinase system and cardiomyopathy.

Changes in the creatine kinase system, cellular energetics, regulation of respiration and alterations in parameters of contractility in experimental animals (myopathic hamsters), and in patients with dilated cardiomyopathy were studied. 31P-NMR methods were used to show that cardiomyopathic hearts are characterized by decreased work index, lower tissue ATP, phosphocreatine, and total creatine contents and diminished creatine kinase activity and energy fluxes. In isolated mitochondria, only the creatine kinase activity was decreased. Both in cardiomyopathic hamsters and human hearts a share of mitochondrial creatine kinase in the total tissue enzyme activity was decreased from 33% to 18% and that of BB elevated from 5% in control to 20%, at an unchanged relative level of MM. In saponins-skinned cardiac fibers on cardiomyocytes creatine (Cr, 25 mM) decreased Km for ADP in regulation of respiration from 133 +/- 20 to 20 +/- 4 microM due to activation of coupled mitochondrial creatine kinase-oxidative phosphorylation reactions in control hamster hearts. In the case of cardiomyopathy it decreased Km for ADP only to 81 +/- 13 microM. In endocardial biopsy samples from the hearts of patients with dilated cardiomyopathy taken during angiography, creatine stimulated respiration was decreased by 36% of control value, which correlated well with increase of end-diastolic pressure and fall in ejection fraction. Thus, changes in mitochondrial creatine kinase expression diminished the efficiency of cellular regulation of respiration in cardiomyopathic hearts that may have functional consequences for hemodynamics or may be adaptive alterations in response to decreased contractility.