1,721,204 research outputs found
Unconventional approaches to diabetes screening: Rejuvenation time for cardiovascular prevention strategies?
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ENDOTHELIAL SIRT6 BLUNTS STROKE SIZE AND NEUROLOGICAL DEFICIT BY PRESERVING BLOOD-BRAIN BARRIER INTEGRITY: A TRANSLATIONAL STUDY
No full textAims: Aging is an established risk factor for stroke; genes regulating longevity are implicated in the pathogenesis of ischaemic stroke where to date, therapeutic options remain limited. The blood-brain barrier (BBB) is crucially involved in ischaemia/reperfusion (I/R) brain injury thus representing an attractive target for developing novel therapeutic agents. Given the role of endothelial cells in the BBB, we hypothesized that the endothelial-specific expression of the recently described longevity gene SIRT6 may exhibit protective properties in stroke.
Methods and results: SIRT6 endothelial expression was reduced following stroke. Endothelial-specific Sirt6 knockout (eSirt6-/-) mice, as well as animals in which Sirt6 overexpression was post-ischaemically induced, underwent transient middle cerebral artery occlusion (tMCAO). eSirt6-/- animals displayed increased infarct volumes, mortality, and neurological deficit after tMCAO, as compared to control littermates. Conversely, post-ischaemic Sirt6 overexpression decreased infarct size and neurological deficit. Analysis of ischaemic brain sections revealed increased BBB damage and endothelial expression of cleaved caspase-3 in eSIRT6-/- mice as compared to controls. In primary human brain microvascular endothelial cells (HBMVECs), hypoxia/reoxygenation (H/R) reduced SIRT6 expression and SIRT6 silencing impaired the barrier function (transendothelial resistance) similar to what was observed in mice exposed to I/R. Further, SIRT6-silenced HBMVECs exposed to H/R showed reduced viability, increased cleaved caspase-3 expression and reduced activation of the survival pathway Akt. In ischaemic stroke patients, SIRT6 expression was higher in those with short-term neurological improvement as assessed by NIHSS scale and correlated with stroke outcome.
Conclusion: Endothelial SIRT6 exerts a protective role in ischaemic stroke by blunting I/R-mediated BBB damage and thus, it may represent an interesting novel therapeutic target to be explored in future clinical investigation
Longevity-associated variant BPIFB4 gene transfer to recapitulate healthy ageing in patients at risk: is the future around the corner?
No full textT-cells in myocardial infarction: Culprit instigators or mere effectors?
No full textImmune system activation and dysfunction characterize the early phase of reperfusion after a myocardial infarction (MI). Despite initially neglected, adaptive immunity has been recently showed to play an important role in this setting. In fact, the immune system can recognize sequestered antigens released by the necrotic tissue, initiating a deleterious autoimmune vicious circle leading to worse outcome. In their recent work, Angelini et al shed the light on a new feature of post-MI which involves two "old players" of post-ischemic myocardial injury: CD31 and matrix metalloproteinase (MMP)-9. Specifically, the authors showed that an enhancement of MMP-9 release could determine the cleavage of inhibitory CD31 from CD4+ T-cells surface in patients with Acute Coronary Syndromes (ACS). These findings open the room for new studies investigating the role of MMP9 in other pathological processes associated with a reduction of CD31 functionality, such as plaque instability and rupture. Of interest, in the case of a causative role for CD31 shedding in ACS would be confirmed, there might be a potential role for the administration of CD31 protein or analogue compounds to blunt post-ischemic cardiac inflammation and improve ACS outcome
Physical activity to reduce PCSK9 levels
No full textThe amount of physical activity (PA) people practice everyday has been reducing in the last decades. Sedentary subjects tend to have an impaired lipid plasma profile with a higher risk of atherosclerosis and related cardio- and cerebrovascular events. Regular PA helps in both primary and secondary cardiovascular prevention because of its beneficial effect on the whole metabolism. Several studies reported lower levels of plasma lipids in trained subjects, but the precise mechanisms by which PA modulates lipoproteins remain only partially described. Thereupon, proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serin protease whose main function is to reduce the amount of low-density lipoprotein cholesterol (LDL-C) receptors, with the direct consequence of reducing LDL-C uptake by the liver and increasing its circulating pool. Accordingly, recently developed PCSK9 inhibitors improved cardiovascular prevention and are increasingly used to reach LDL-C goals in patients at high CV risk. Whether PA can modulate the levels of PCSK9 remains partially explored. Recent studies suggest PA as a negative modulator of such a deleterious CV mediator. Yet the level of evidence is limited. The aim of this review is to summarize the recent reports concerning the regulatory role of PA on PCSK9 plasma levels, highlighting the beneficial role of regular exercise on the prevention of atherosclerosis and overall CV health
Inflammatory biomarkers as cost-effective predictive tools in metabolic dysfunction-associated fatty liver disease
No full textQu and Li emphasize a fundamental aspect of metabolic dysfunction-associated fatty liver disease in their manuscript, focusing on the critical need for noninvasive diagnostic tools to improve risk stratification and predict the progression to severe liver complications. Affecting approximately 25% of the global population, metabolic dysfunction-associated fatty liver disease is the most common chronic liver condition, with higher prevalence among those with obesity. This letter stresses the importance of early diagnosis and intervention, especially given the rising incidence of obesity and metabolic syndrome. Research advancements provide insight into the potential of biomarkers (particularly inflammation-related) as predictive tools for disease progression and treatment response. This overview addresses pleiotropic biomarkers linked to chronic inflammation and cardiometabolic disorders, which may aid in risk stratification and treatment efficacy monitoring. Despite progress, significant knowledge gaps remain in the clinical application of these biomarkers, necessitating further research to establish standardized protocols and validate their utility in clinical practice. Understanding the complex interactions among these factors opens new avenues to enhance risk assessment, leading to better patient outcomes and addressing the public health burden of this worldwide condition
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