Hemorrhagic transformation of acute ischemic stroke is limited in hypertensive patients with cardiac hypertrophy

BACKGROUND: It has been clearly demonstrated that hypertension and one of its main evoked effects, cardiac hypertrophy, are independent risk factors for ischemic stroke. However, the ischemic brain lesions can further be affected by a second wave of injury characterized by hemorrhagic transformation (HT) of the primary ischemic lesion, which significantly aggravates the clinical outcome. So far, the risk factors that could affect such a transition in hypertensive patients are still unclear. METHODS: In this study, we investigated whether in hypertensive patients the concomitant presence of cardiac hypertrophy can affect the transition of ischemic brain lesions toward HT. RESULTS: Our analysis was focused on a population of hypertensive patients admitted to our Acute Stroke Unit. The hypertensives with acute ischemic stroke suffering of HT were 18% of the sample. In these latter, the prevalence of cardiac hypertrophy was significantly lower than in those spared by HT as also shown by the levels of left ventricular mass index (LVMI) that were significantly higher in patients spared by HT. More important, cardiac hypertrophy was protective even from symptomatic HT. CONCLUSION: Here we show that hypertensive patients with cardiac hypertrophy have less probability to develop HT during an acute episode of ischemic stroke. These results could help to identify patients with lower risk of spontaneous HT and that could have better beneficial effects from thrombolytic therapy during acute ischemic stroke

Brain MRI fiber-tracking reveals white matter alterations in hypertensive patients without damage at conventional neuroimaging

Hypertension is one of the main risk factor for dementia. The subtle damage provoked by chronic high blood pressure in the brain is usually evidenced by conventional magnetic resonance imaging (MRI), in terms of white matter (WM) hyperintensities or cerebral atrophy. However, it is clear that by the time brain damage is visible, it may be too late hampering neurodegeneration. Aim of this study was to characterize a signature of early brain damage induced by hypertension, before the neurodegenerative injury manifests

Mechanisms of soluble beta-amyloid impairment of endothelial function

Alzheimer's disease ( AD) has been recently associated with vascular risk factors. beta-amyloid peptides (AbetaP), the main component of senile plaques typical of AD, circulate in soluble globular form in bloodstream. Interestingly, AbetaP is able to induce endothelial dysfunction, and this effect may represent the link between vascular and neuronal pathophysiological factors involved in AD. We aimed to clarify the molecular mechanisms underlying globular AbetaP-induced vascular toxicity. Using several methodological approaches, we have observed that in vascular tissues globular AbetaP is unable to induce oxidative stress, one of the mechanisms hypothesized involved in beta-amyloid toxicity. More important, we have demonstrated that globular AbetaP is able to localize on vascular endothelium, where it inhibits eNOS enzymatic activity. In particular, AbetaP enhances eNOS phosphorylation on threonine 495 and serine 116 and reduces acetylcholine-induced phosphorylation on serine 1177. Such an effect depends on a PKC signaling pathway, as suggested by its phosphorylation on serine 660. In fact, selective inhibition of the calcium-dependent group of PKC is able to rescue beta-amyloid-induced alteration of eNOS phosphorylation, NO production, and endothelial vasorelaxation. The activation of these Ca2+-dependent pathways is probably due to the ability of AbetaP to evoke Ca2+ leakage from inositol 1,4,5-triphosphate receptors on endoplasmic reticulum. Our data demonstrate that globular AbetaP-induced endothelial NO dysfunction can be attributed to an alteration of intracellular Ca2+ homeostasis, which could lead to the activation of calcium-dependent group of PKC with a consequent change of the eNOS phosphorylation pattern. These mechanisms could contribute to shed further light on the toxic effect of beta-amyloid in vascular tissues