Circulatory Maternal Endothelin 1 and Matrix Metalloproteinase-9 Gene Expression in PREECLAMPSIA: A Study in Western Uttar Pradesh, India.

Introduction: Preeclampsia (PE) is a multiorgan disease of pregnant women. The main pathophysiology of PE is a trophoblastic invasion into maternal circulation leading to alterations in circulatory levels of matrix metalloproteinases (MMPs), inflammatory markers, and endothelin 1(ET1) levels. Therefore, the present study has explored the role of MMP-9 and ET1 and their association in PE. The advantage of the study is to provide insight into the pathology of PE. These markers may help in the early diagnosis and prognosis of PE. Objective: To investigate MMP-9 gene expression, ET1 level in PE cases and their correlation with blood pressure (BP), gestational age, weight, and height. Methods: The study design was a case-control observational study, which included 70 subjects in each case (PE) and controls (normal pregnant women (NPW)). Whole blood (250 ul) was utilized for RNA extraction (Trizol method) and synthesized cDNA as per manufacturer protocol. MMP-9 gene expression was analyzed by real-time PCR. Serum was utilized for ET1 estimation by sandwich ELISA. Results: The ET1 levels and MMP-9 gene expression were significantly increased in preeclamptic women as compared to controls. There was no significant correlation between MMP-9 gene expression and serum ET1 levels. However, a significant moderate association between systolic BP and diastolic BP with ET1 levels and MMP9 gene expression was seen in both PE and NPW. Conclusion: A significantly increased circulatory concentration of ET1 and MMP-9 gene expression in PE might be used as an early diagnostic as well as a prognostic marker of PE.

The study of markers of endothelial dysfunction in metabolic syndrome.

BACKGROUND: Metabolic syndrome (MetS) consists of a constellation of metabolic abnormalities that confer increased risk of cardiovascular disease (CVD) and diabetes mellitus (DM). Endothelial dysfunction is one of the key components of MetS which is caused by imbalance between vasodilatory substances like nitric oxide (NO) and vaso-constrictive substances like endothelin and prothrombotic factors like plasminogen activator inhibitor-1 (PAI-1). OBJECTIVE: To study the markers of endothelial dysfunction (NO and endothelin) and prothrombotic markers (PAI-1) among the study subjects. MATERIALS AND METHODS: We enrolled 50 diagnosed cases of MetS as per International Diabetes Federation (IDF) criteria and 50 healthy volunteers as controls. Clinical evaluation included anthropometric, routine biochemical, hematological, serum insulin, NO, endothelin and PAI-1 measurements. RESULTS: Subjects with MetS had higher insulin, endothelin and PAI-1 levels and low NO levels as compared to controls and the difference was found to be significant. The serum insulin levels were positively correlated with PAI-1 and endothelin, and negatively correlated with NO. CONCLUSION: Endothelial functional status as reflected by decreased NO and increased serum endothelin levels along with insulin resistance is seen in MetS. Moreover, higher serum level of PAI-1 also tilts towards a more prothrombotic milieu in the vascular endothelium. Hence endothelial dysfunction and prothrombotic markers may be used to guide for early diagnosis of cardiovascular disease and type 2 diabetes in patients with MetS.

Imbalance between protective (adiponectin) and prothrombotic (Plasminogen Activator Inhibitor-1) adipokines in metabolic syndrome.

AIMS: The metabolic syndrome (MS) consists of a constellation of metabolic abnormalities that confer increased risk of cardiovascular disease (CVD) and diabetes mellitus (DM). Visceral adipose tissue actively produces a variety of adipokines that interact in various obesity related disorders such as metabolic syndrome, diabetes mellitus and heart diseases. Adiponectin has protective role in the vascular physiology while Plasminogen Activator Inhibitor-1 (PAI-1) has a prothrombotic and consequent deleterious effect on the endothelium. We attempted to assess the putative imbalance if any between these two mediators in subjects with metabolic syndrome in the Indian context. MATERIALS AND METHODS: We enrolled 50 diagnosed case of metabolic syndrome as per International Diabetes Federation (IDF) criteria and 50 healthy volunteers as control. Clinical evaluation included anthropometric, routine biochemical analysis as well as adiponectin and PAI-1 measurement. RESULT: Subject with MS had significantly lower adiponectin (9.8±1.0 vs 16±1.1 µg/ml) and higher PAI-1 (232±87 vs 185±96 ng/ml). A statistically significant correlation was observed between adiponectin and HDL levels (r=0.388, p=0.005). CONCLUSION: Subjects with MS have lower adiponectin and higher PAI-1 levels as compared to controls. The subsequent tilt toward a more prothrombotic and pro inflammatory milieu in the vascular endothelium may be pathognomonic of metabolic syndrome. This understanding of the still undiscovered subtle vascular alterations may help in the better management of obesity and MS.