Askar Mohammad

Collateral blood vessels in acute ischaemic stroke: a potential therapeutic target

Ischaemic stroke results from acute arterial occlusion leading to focal hypoperfusion. Thrombolysis is the only proven treatment. Advanced neuroimaging techniques allow a detailed assessment of the cerebral circulation in patients with acute stroke, and provide information about the status of collateral vessels and collateral blood flow, which could attenuate the effects of arterial occlusion. Imaging of the brain and vessels has shown that collateral flow can sustain brain tissue for hours after the occlusion of major arteries to the brain, and the augmentation or maintenance of collateral flow is therefore a potential therapeutic target. Several interventions that might augment collateral blood flow are being investigated.

Homocysteine Reduces Endothelial Progenitor Cells in Stroke Patients through Apoptosis

Homocysteine (Hcy) is a risk factor for vascular dysfunction. High levels of Hcy may result in vascular injury accelerating atherosclerosis leading to ischemia. After ischemia, endothelial progenitor cells (EPCs) migrate from bone marrow to repair damaged sites either through direct incorporation of EPCs or by repopulating mature endothelial cells. This study looks into the relationship between increased Hcy in patients with cerebrovascular disease (CVD) and EPCs. Some patients with hyperhomocysteinemia were treated with B vitamins to evaluate if the treatment reverses the elevated Hcy and its impact on their EPC levels. EPCs were treated with Hcy to determine the in vitro effects of Hcy. Our clinical findings show that elevated Hcy levels have an inverse relationship with EPC levels and B vitamin intervention can reverse this effect. Our in vitro work shows that Hcy-mediated EPC toxicity is due to apoptosis involving caspase-8, cytochrome c release, and caspase-3 activation. Vitamin B6, and B9 significantly impair Hcy-mediated EPC caspase-3 activation in vitro. Our clinical and in vitro data together indicate that increased Hcy results in a decrease in EPC numbers. This decrease in EPC by Hcy may be occurring through increased apoptosis and B vitamins (B6, B9) intervention can attenuate such effects.

Circulating endothelial progenitor cells and age-related white matter changes

Background and Purpose— The objective was to evaluate the relationship between circulating endothelial progenitor cells (EPC) and age-related white matter changes (ARWMC). Endothelial dysfunction plays a role in the development of ARWMC. EPC incorporate into sites endothelial damage and are thought to be involved in the repair of vascular risk factor induced endothelial injury. ARWMC can be evaluated using CT or MRI. Methods— In 172 individuals, circulating EPC were defined by the surface markers CD31 and von Willebrand factor. ARWMC were rated on CT scan using the ARWMC scale and divided into 3 groups based on ARWMC scale score (ARWMC score 0 [none], score 1–10 [mild-to-moderate], score >10 [severe]). Severity of ARWMC was correlated with levels of EPC and vascular risk factors. Results— On univariate analysis, EPC were found to be significantly lower in patients with severe ARWMC (P=0.01). ARWMC were also associated with hypertension (P<0.001), age (P<0.001), creatinine clearance (P=0.031), C-reactive protein (P<0.001), and use of angiotensin-converting enzyme or angiotensin receptor blocker (P=0.004). Multiple logistic regression analysis identified EPC level, age, hypertension, and hypertriglyceridemia as significant independent predictors of severe ARWMC. Conclusions— Levels of circulating EPC were significantly lower in patients with severe ARWMC. Other variables significantly associated with severe ARWMC were age, hypertension, and hypertriglyceridemia. Further study is required to delineate the pathophysiological relationship between EPC, vascular risk factors, and ARWMC.

Hyperthermia up-regulates matrix metalloproteinases and accelerates basement membrane degradation in experimental stroke

Increased body temperature results in severe neuronal damage during cerebral ischemia. We hypothesized that hyperthermia hastens the degradation of basement membrane protein components and causes the disruption of brain microvasculature through early up-regulation of matrix metalloproteinases (MMPs). In this study, we present data from both non-ischemic and ischemic hemispheres of stroke induced rat brain. We found that the expression of MMP-2 and -9 and degradation of laminin and collagen IV were significantly increased in the ischemic hemisphere when compared with the non-ischemic hemisphere after 24h of normothermic stroke (p<0.001). No significant increase in MMPs expression and basement membrane components degradation was observed after 4h of normothermic stroke. At 4h, hyperthermia increased the expression of MMP-2 and -9 and subsequent degradation of laminin and collagen IV at the level that was comparable to normothermic stroke after 24h and significantly higher than 4h of normothermic stroke (p<0.001). The early increase in MMPs may be an important contributing factor to the severe neuronal damage evident with hyperthermia during an ischemic stroke.

Endothelial progenitor cells in patients with acute cerebrovascular ischemia.

OBJECTIVE Statins have been shown to increase endothelial progenitor cells (EPCs) in patients with cardiovascular disease. However, there is no similar study that has been done on the patients recovering from cerebrovascular disease. We present the largest prospective study of statin therapy on EPC levels of patients recovering from stroke. METHOD Our study subjects were treated with rosuvastatin (10 mg/day) over a period of 12 weeks. Blood was collected from these patients periodically and EPC levels were measured along with other biochemical parameters. RESULTS AND CONCLUSIONS Our study shows that rosuvastatin treatment significantly reduces the low density lipoprotein (LDL) levels in the patients over the 12 weeks. However, we did not find any corresponding changes in the EPC levels during this time period. Earlier reports indicated that statin use could increase EPC proliferation. Our research, however, indicates that the in-vivo effects of rosuvastatin are not similar to those of previous reports. There may be several reasons for this lack of congruence between these two studies, including age of the study population, predominantly low high density lipoprotein (HDL) levels in our subjects and effects from other concomitant medications.

Endothelial progenitor cells and vascular disease Are they for real

Endothelial progenitor cells (EPCs) were initially described in 1997, though their properties and roles are still being investigated and debated. Their core characteristics were identified as circulating cells displaying a variety of cell surface proteins thought to be endothelial specific, the ability to grow in culture, and the ability to localize and promote vascular growth at sites of ischemia.1 Very soon thereafter, studies suggested an inverse relationship between the number of circulating EPCs and vascular risk factors in patients with stable ischemic heart disease2 and, later, in those with acute or stable stroke.3 Subsequent reports suggested that the use of statins could increase EPC numbers in patients with stable coronary artery disease, though this observation was not confirmed in a larger randomized trial.4 Other data suggested that infusion of EPCs after an acute myocardial infarction could result in improvement in cardiac function and decreased mortality.5 The initial excitement, not surprisingly, prompted numerous investigations on EPCs. However, despite 13 years having passed since the landmark article in Science ,1 and having done further, more detailed, analyses on EPCs, we are still …