Mohammad Z Ashraf

Apolipoprotein A-I (apoA-I) is cross-linked and dysfunctional in human atheroma. Although multiple mechanisms of apoA-I cross-linking have been demonstrated in vitro, the in vivo mechanisms of cross-linking are not well established. We have recently demonstrated the highly selective and efficient modification of high-density lipoprotein (HDL) apopr...

Abstract Introduction: High altitude hypoxia exacerbates deep vein thrombosis (DVT) via activation of coagulation factors. Acute hypoxia during altitude exposures is associated with decreased natural anticoagulants, one such is thrombomodulin (TM), primarily expressed by endothelial cells. Hypoxia has been associated to DNA methylation as well. He...

Background: The pathophysiology of Deep vein thrombosis (DVT) is considered as multifactorial, where thrombus formation is interplay of genetic and acquired risk factors. Lately, different pipelines have been developed to identify novel lncRNAs in different diseases, however a little is known about the expression profile and roles of lncRNAs in hum...

MicroRNAs (miRNAs) are involved in a wide variety of cellular processes and post-transcriptionally regulate several mechanism and diseases. However, contribution of miRNAs functioning during hypoxia and DNA methylation together is less understood. The current study was aimed to find a shared miRNAs signature upstream to hypoxia (via HIF gene family...

Currently available anticoagulants for prevention and treatment of thrombosis have several limitations, thus, small organic scaffolds that can dissolve clots in vivo in a dose dependent manner with lesser side effects are highly desirable. Here we report the synthesis of esculin pentasulfate (EPS) and assessment of its in vitro, in vivo and ex vivo...

Venous thromboembolism (VTE), a multi-factorial disease, is the third most common cardiovascular disease. Established genetic and acquired risk factors are responsible for the onset of VTE. High altitude (HA) also poses as an additional risk factor, predisposing individuals to VTE; however, its molecular mechanism remains elusive. This study aimed...

Venous thromboembolism (VTE), the third leading cardiovascular complication, requires more understanding at molecular levels. Here, we have identified miR-145 as a key molecule for regulating thrombus formation in venous thrombosis (VT) employing network based bioinformatics approach and in vivo experiments. Levels of miR-145 showed an inverse corr...

Thrombosis is a leading cause of morbidity and mortality in patients with myeloproliferative disorders (MPDs), particularly polycythemia vera (PV) and essential thrombocythemia (ET). Despite the attempts to establish a link between them, the shared biological mechanisms are yet to be characterized. An integrated gene expression meta-analysis of fiv...

Objectives: Genes related to endothelial function are responsible for the regulation of vascular functions. Aim: The aim of this study is to investigate whether endothelial gene-associated polymorphism and their plasma levels can be used to predict the risk for venous thromboembolism (VTE). Methods: We studied 133 patients with VTE and 164 hea...

Hypertension Research, official publication of the Japanese Society of Hypertension, publishes papers reporting original clinical and experimental research in the field of hypertension and related cardiovascular diseases.

Objective: Besides well known predisposing conditions such as cancer, diabetes, cardiovascular disease and surgery; hypoxia per se has been suggested to be an additional risk factor for venous thrombosis (VT). We have recently shown that hypoxia, either localized due to stasis, or systemic, due to environmental factors such as high altitude exposur...

Introduction The increased risk of thromboembolic events under low oxygen environments such as high altitude regions is a well known phenomenon but with little knowledge about molecular events underlying its pathogenesis. We have recently reported the proteomic changes in hyperreactive platelets under hypoxia and demonstrated that increased activit...

Introduction The increased risk of thromboembolic events under low oxygen environments such as high altitude regions is a well known phenomenon but with little knowledge about molecular events underlying its pathogenesis. We have recently reported the proteomic changes in hyperreactive platelets under hypoxia and demonstrated that increased activit...

The genetic variants linked with the susceptibility of individuals to VTE are well known; however, the studies explaining the ethnicity based difference in susceptibility to VTE are limited. Present study assesses mutations in six candidate genes contributing to the etiology of VTE in Indian subjects. The study comprised 93 VTE patients and 102 hea...

Physiological hemostatic balance is a coordinated outcome of counteracting coagulation and fibrinolytic systems. An imbalance of procoagulant and anticoagulant factors may result in life threatening thromboembolism. Presently, anticoagulant administration is the first line of therapy for the treatment of these conditions and several anticoagulants...

Key Points Hypoxia induces altered platelet proteome/reactivity, which correlates with a prothrombotic phenotype. CAPNS1-dependent calpain activity in platelet activation cascade is associated with hypoxia-induced thrombogenesis.

Stroke in the young is attributed to the prevalence of thrombophilia, however, reports explaining the cause mechanisms from Indian populations are largely not known. The information about the association of inherited thrombophilia and occurrence of stroke is still missing. Therefore, we describe here 52 cases of young ischemic stroke of which 22 ca...

Abstract The scavenger receptor (SR) super family consists of integral membrane glycoproteins that are involved in recognition of polyanionic structures of either endogenous (e.g., oxidized low-density lipoprotein) or exogenous (e.g., bacterial lipopolysaccharides) origin. SRs are structurally diverse and can be classified into seven different clas...

There are several genetic and acquired risk factors for venous thromboembolism. Exposure to high altitude (HA), either during air travel, ascension of mountains, or while engaging in sports activities, has been observed to result in a hypercoagulable state, thus predisposing to thromboembolic events. Although several previous studies have suggested...

Studies on different populations have suggested variability in individual susceptibility to altitude sickness depending on genetic makeup. The renin-angiotensin-aldosterone system (RAAS) pathway plays a key role in regulation of vascular tone and circulatory homeostasis. The present study was undertaken to investigate the possible association of th...

Scavenger receptors are modified lipoprotein binding receptors, expressed on the surface of a variety of cells including endothelial, macrophages and platelets. The most extensively studied class B scavenger receptors comprise of CD36 and SR-BI and have been found to bind to native and modified LDL. Interaction of modified LDL to CD36 accelerates f...

Hypercholesterolemia is associated with increased platelet sensitivity to agonists and a prothrombotic phenotype. Mechanisms of platelet hypersensitivity are poorly understood; however, increased platelet cholesterol levels associated with hypercholesterolemia were proposed as leading to hypersensitivity. Scavenger receptor class B type I (SR-BI) i...

Multiple protein kinases have been implicated in cardiovascular disease; however, little is known about the role of their counterparts: the protein phosphatases. To test the hypothesis that mitogen-activated protein kinase phosphatase (MKP)-1 is actively involved in atherogenesis. Mice with homozygous deficiency in MKP-1 (MKP-1(-/-)) were bred with...

Specific oxidized phospholipids (oxPC(CD36)) accumulate in vivo at sites of oxidative stress and serve as high affinity ligands for scavenger receptors class B (CD36 and SR-BI). Recognition of oxPC(CD36) by scavenger receptors plays a role in several pathophysiological processes. The structural basis for the recognition of oxPC(CD36) by CD36 and SR...

Biologically active oxidized phospholipids can initiate and modulate many of the cellular events attributed to inflammation leading to atherosclerosis. Produced by enzymatic or non-enzymatic processes, these molecules interact with various cells via specific receptors and in general give rise to inflammatory signals. There is considerable evidence...

We have recently demonstrated that specific oxidized phospholipids (oxPC(CD36)) accumulate at sites of oxidative stress in vivo such as within atherosclerotic lesions, hyperlipidemic plasma, and plasma with low high-density lipoprotein levels. oxPC(CD36) serve as high affinity ligands for the scavenger receptor CD36, mediate uptake of oxidized low...

Recent studies have identified a novel family of oxidized phosphatidylcholines (oxPC(CD36)) that serve as highly specific ligands for scavenger receptor CD36. oxPC(CD36) accumulate in vivo and mediate macrophage foam cell formation as well as promote platelet hyper-reactivity in hyperlipidemia via CD36. The structural basis of oxPC(CD36) binding to...

Oxidatively modified LDL (OxLDL) and HDL (OxHDL) are present in the intima of atheromatous plaques and in plasma. While prothrombotic activity of OxLDL mediated by platelet CD36 is established, the role of oxHDL in thrombosis is not known. We now report that OxHDL, but not native HDL, is a potent inhibitor of platelet activation and aggregation ind...

Oxidatively modified LDL (OxLDL) and HDL (OxHDL) are present in the intima of atheromatous plaques and in plasma. While prothrombotic activity of OxLDL mediated by platelet CD36 is established, the role of oxHDL in thrombosis is not known. We now report that OxHDL, but not native HDL, is a potent inhibitor of platelet activation and aggregation ind...

Numerous studies have reported the presence of oxidatively modified high-density lipoprotein (OxHDL) within the intima of atheromatous plaques as well as in plasma; however, its role in the pathogenesis of thrombotic disease is not established. We now report that OxHDL, but not native HDL, is a potent inhibitor of platelet activation and aggregatio...

The mechanisms underlying the impairment of endothelium-mediated vasorelaxation induced by dietary hypercholesterolemia and the mechanisms of restoration of endothelial function following reintroduction of low cholesterol diet were evaluated. Feeding rats with high cholesterol diet induced hypercholesterolemia and high blood pressure. This was asso...

The homeobox gene HOXA9 has recently been shown to be an important regulator of endothelial cell (EC) differentiation and activation in addition to its role in embryonic development and hematopoiesis. In this report, we have determined that the EC-leukocyte adhesion molecule E-selectin is a key target for HOXA9. The depletion of HOXA9 protein in EC...

Protections of endothelial integrity by elimination of certain risk have proven to be effective in maintaining hemostasis and in slowing the progress of the cardiovascular disease. Indigenous drugs are the natural source of protection against these disorders, which can be used more effectively by the knowledge of their active ingredients as well as...

The vasorelaxant effect of garlic (Alium sativum L.) has been suggested to be partially mediated through endothelium. The present study was designed to evaluate the role of various endothelium-mediated mechanisms in vasorelaxant response of garlic on isolated aortic rings of rats. In tissues precontracted with phenylephrine (PE) 10(-6)M, concentrat...

The contractility of airway smooth muscle (ASM) plays an important role in pathophysiology of several bronchial disorders. Increased contraction of ASM during asthma and respiratory viral infection has been attributed to the release of mediators acting through different receptors. In the present study, influence of influenza type A virus (H1N1) inf...

The present study was undertaken to examine the endothelium modulated effects of polypharmaceutical drug lipotab and its individual ingredients in isolated aortic rings of rat. Endothelium intact and denuded aortic rings were precontracted with phenylephrine 10(-6) M and drugs were added in cumulative manner in concentration ranging from 1 to 50 mi...