1,298 research outputs found
Longevity-associated variant BPIFB4 gene transfer to recapitulate healthy ageing in patients at risk: is the future around the corner?
No full textThe Role of Vascular Aging in Atherosclerotic Plaque Development and Vulnerability
No full textBACKGROUND
The ongoing demographical shift is leading to an unprecedented aging of the population. As a consequence, the prevalence of age-related diseases, such as atherosclerosis and its thrombotic complications is set to increase in the near future. Endothelial dysfunction and vascular stiffening characterize arterial aging and set the stage for the development of cardiovascular diseases. Atherosclerotic plaques evolve over time, the extent to which these changes might affect their stability and predispose to sudden complications remains to be determined. Recent advances in imaging technology will allow for longitudinal prospective studies following the progression of plaque burden aimed at better characterizing changes over time associated with plaque stability or rupture. Oxidative stress and inflammation, firmly established driving forces of age-related CV dysfunction, also play an important role in atherosclerotic plaque destabilization and rupture. Several genes involved in lifespan determination are known regulator of redox cellular balance and pre-clinical evidence underlines their pathophysiological roles in age-related cardiovascular dysfunction and atherosclerosis.
OBJECTIVE
The aim of this narrative review is to examine the impact of aging on arterial function and atherosclerotic plaque development. Furthermore, we report how molecular mechanisms of vascular aging might regulate age-related plaque modifications and how this may help to identify novel therapeutic targets to attenuate the increased risk of CV disease in elderly people
IL-1β and Statin Treatment in Patients with Myocardial Infarction and Diabetic Cardiomyopathy
Full text linkStatins are effective lipid-lowering drugs with a good safety profile that have become, over the years, the first-line therapy for patients with dyslipidemia and a real cornerstone of cardiovascular (CV) preventive therapy. Thanks to both cholesterol-related and "pleiotropic" effects, statins have a beneficial impact against CV diseases. In particular, by reducing lipids and inflammation statins, they can influence the pathogenesis of both myocardial infarction and diabetic cardiomyopathy. Among inflammatory mediators involved in these diseases, interleukin (IL)-1β is a pro-inflammatory cytokine that recently been shown to be an effective target in secondary prevention of CV events. Statins are largely prescribed to patients with myocardial infarction and diabetes, but their effects on IL-1β synthesis and release remain to be fully characterized. Of interest, preliminary studies even report IL-1β secretion to rise after treatment with statins, with a potential impact on the inflammatory microenvironment and glycemic control. Here, we will summarize evidence of the role of statins in the prevention and treatment of myocardial infarction and diabetic cardiomyopathy. In accordance with the dual lipid-lowering and anti-inflammatory effect of these drugs and in light of the important results achieved by IL-1β inhibition through canakinumab in CV secondary prevention, we will dissect the current evidence linking statins with IL-1β and outline the possible benefits of a potential double treatment with statins and canakinumab
Ageing and longevity genes in cardiovascular diseases
No full textOver the last century, Western societies experienced a demographic shift driven by increased lifespan and decreased fertility, resulting in the subversion of the world's demographic pyramid. In ageing societies, cardiovascular diseases are the major cause of morbidity and mortality, thus representing a major societal and economic burden. Indeed, ageing associates with the deterioration of a genetic network implicated in senescence and longevity, orchestrating deleterious cellular processes that converge in the structural and functional decline of both the myocardium and the vasculature. In this review, we revise a compendium of genes involved in these processes and delineate possible strategies to interfere with them. Dietary interventions (eg intermittent fasting) and sirtuin-activating compounds are among the most promising interventions shown to promote protective effects on the ageing cardiovascular system. We conclude that ageing and longevity genes modulate cardiovascular function by acting on deleterious downstream processes such as inflammation and oxidative stress, thus representing promising targets for the prevention and treatment of age-related cardiovascular dysfunction
Camici bianchi e tute blu
No full textSul finire degli anni settanta, mentre le nostre facoltà universitarie vanno avvitandosi nella loro crisi, una parte del mondo accademico si rende conto dell’inadeguatezza di pratiche didattiche massificate e comincia a promuovere sporadiche iniziative di segno contrario: rapide, intense, ad alta densità di interconnessione tra docenti e studenti. La necessità di interpretare situazioni complesse rispondendo a diversi interlocutori ha di fatto stimolato una interessante e variegata produzione progettuale, nella quale tutti noi, tolto il camice bianco e indossata la tuta blu, abbiamo trovato il modo di immergerci nella sperimentazione e “sporcare” positivamente le nostre autobiografie
Ischemic stroke across sexes: What is the status quo?
No full textStroke prevalence is expected to increase in the next decades due to the aging of the Western population. Ischemic stroke (IS) shows an age- and sex-dependent distribution in which men represent the most affected population within 65 years of age, being passed by post-menopausal women in older age groups. Furthermore, a sexual dimorphism concerning risk factors, presentation and treatment of IS has been widely recognized. In order to address these phenomena, a number of issue have been raised involving both socio-economical and biological factors. The latter can be either dependent on sex hormones or due to intrinsic factors. Although women have poorer outcomes and are more likely to die after a cerebrovascular event, they are still underrepresented in clinical trials and this is mirrored by the lack of sex-tailored therapies. A greater effort is needed in the future to ensure improved treatment and quality of life to both sexes
Enhanced age-dependent cerebrovascular dysfunction is mediated by adaptor protein p66Shc
No full textBACKGROUND: Aging is an independent risk factor for cardiovascular and cerebrovascular disease. To date, little is known about the mechanisms of aging of cerebral arteries and whether the aging gene p66(Shc) is implicated in it. The present study was designed to assess age-induced vascular dysfunction in cerebral and systemic arteries of wild type (wt) and p66(Shc-/-) mice.
METHODS: Basilar arteries and size matched second order femoral arteries of 3-month (3M), 6-month (6M) and 2-year old (2Y) mice were studied in wt and p66(Shc-/-) mice. To assess vascular function, arterial rings mounted in a myograph for isometric tension recordings were exposed to increasing concentrations of acetylcholine and sodium nitroprusside. Reactive oxygen species (ROS) generation was assessed in femoral and basilar arteries using the spin trap 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine.
RESULTS: In wt mice, endothelial function of the femoral artery was not affected by age unlike in the basilar artery where an age-dependent dysfunction was observed. In p66(Shc-/-) a similar response was observed in the femoral artery; however, age-dependent endothelial dysfunction of the basilar artery was blunted as compared to wt. Levels of ROS were comparable in the femoral arteries of 3M and 2Y of wt and p66(Shc-/-) mice. Differently, ROS levels in the basilar artery of wt mice were strongly increased by age unlike in p66(Shc-/-) mice where they remained comparable irrespective of age.
CONCLUSIONS: Endothelial function in cerebral arteries, but not in size-matched systemic ones, is heavily impaired by aging. This process is paralleled by an increased ROS production and is mediated by the p66(Shc) gene
Cytokines as therapeutic targets for cardio- and cerebrovascular diseases
No full textDespite major advances in prevention and treatment, cardiac and cerebral atherothrombotic complications still account for substantial morbidity and mortality worldwide. In this context, inflammation is involved in the chronic process leading atherosclerotic plaque formation and its complications, as well as in the maladaptive response to acute ischemic events. For this reason, modulation of inflammation is nowadays seen as a promising therapeutic strategy to counteract the burden of cardio- and cerebrovascular disease. Being produced and recognized by both inflammatory and vascular cells, the complex network of cytokines holds key functions in the crosstalk of these two systems and orchestrates the progression of atherothrombosis. By binding to membrane receptors, these soluble mediators trigger specific intracellular signaling pathways eventually leading to the activation of transcription factors and a deep modulation of cell function. Both stimulatory and inhibitory cytokines have been described and progressively reported as markers of disease or interesting therapeutic targets in the cardiovascular field. Nevertheless, cytokine inhibition is burdened by harmful side effects that will most likely prevent its chronic use in favor of acute administrations in well-selected subjects at high risk. Here, we summarize the current state of knowledge regarding the modulatory role of cytokines on atherosclerosis, myocardial infarction, and stroke. Then, we discuss evidence from clinical trials specifically targeting cytokines and the potential implication of these advances into daily clinical practice
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