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Background: Transglutaminase 2 (TG2) is an enzyme involved in the pathogenesis of vascular remodeling in conditions of chronic over-nutrition and activation of the renin angiotensin aldosterone system (RAAS). Furthermore, it has been shown that pharmacologic inhibition of TG2 significantly reduces blood pressure in male rodents. However, the cell-specific role of TG2 activation in vascular smooth muscle cells (VSMC) in mediating the hypertensive response to RAAS overactivation has not been explored. Methods: We generated a novel inducible model (tamoxifen dose: 50 mg/kg/d oral for 6 weeks) of TG2 deletion in VSMC (VSMCTG2KO) by sequentially crossing Tgm2t/t floxed mice (loxP sites flanking exons 6-8 of the TG2, C polypeptide [Tgm2] gene) with male Myh11-CreERT2 positive mice. Effectiveness of the TG2 deletion was evaluated by immunohistochemistry and TG2 activity was determined by incorporation of Alexa Fluor488 Cadaverine.A cohort of fifteen-month-old wild-type and VSMC TG2KO male mice were implanted with deoxycorticosterone (DOCA; 50 mg, 21-day releasing pellets) and 1 % salt added to the drinking water. Systolic blood pressure was assessed by tail-cuff method prior to sacrifice. Ex vivo aortic stiffness was determined by atomic force microscopy. Student t-test or two-way ANOVA were used for statistical analysis as appropriate. The results were considered significant when p Results: administration of DOCA/salt induced increases in systolic blood pressure, augmented expression of TG2 in aorta, as well as increased aortic stiffness in wild-type mice (10.47±1.27kPA DOCA/salt vs. 3.91 + 1.01 kPa placebo). The VSMCTG2KO model exhibited 77% downregulation of TG2 expression in VSMC. VSMC TG2 KO suppressed DOCA/salt induced TG2 activity (29.13 + 2.22 arbitrary units (AU) in DOCA/salt vs 14.10 + 2.90 AU in KO cohort). This was accompanied by a significant improvement in DOCA/ salt-induced hypertension (SBP 142 ± 5.4 mmHg in DOCA/salt treated mice vs. 111.8 ± 6.2 mmHg in VSMCTG2KO). Conclusions: Our data demonstrate for the first-time the key role of TG2 activation in VSMC, in the regulation of hypertensive responses in in a male rodent model of RAAS activation.

Obesity continues to increase dramatically in both industrialized and nonindustrialized countries. The scope of the problem in Hispanic populations follows a similar epidemic pattern to industrialized countries, but the unfavorable social and economic features of these populations have placed them at increased risk of developing cardiometabolic syndrome and cardiovascular disease. Some pathophysiologic elements of obesity appear to have a differential biologic behavior in these populations, suggesting that not only environmental factors, but also genetically determined conditions, can influence obesity-related cardiometabolic risk. However, the high epidemiologic diversity of these populations and the lack of reliable statistics make it difficult to ascertain the characteristics of obesity in Hispanics, especially as most of the available data come from Hispanics living in industrialized countries. The management of obesity in Hispanic populations is similar to that in non-Hispanics, and is based on lifestyle changes, weight-reducing medication and bariatric surgery. Novel research related to gut-derived hormones and the endocannabinoid network will potentially contribute to treat obesity better. Newer studies taking into account ethnic differences will result in improved therapeutic alternatives for the prevention of obesity and cardiometabolic syndrome-related cardiovascular disease if they can be coupled with improved living conditions.

Cardiovascular disease (CVD) and Type 2 diabetes mellitus (DM2), once conceived as different entities, share common origins and pathways. Increased activity of the renin-angiotensin-aldosterone-system, insulin resistance, chronic low-grade inflammation and oxidative stress collectively contribute to endothelial dysfunction and atherosclerosis, which manifest clinically as CVD. Nowadays, it is possible to identify and intervene in high-risk populations even before the clinical diagnosis of DM2. The control of dietary patterns and increased physical activity is completely feasible, as well as the management of hypertension and dyslipidaemia. Pharmacological interventions targeted at blocking renin-angiotensin-aldosterone-system and sensitising to insulin have a role in the prevention of DM2 and CVD, and are avidly explored worldwide. In the near future, ongoing trials should provide data that will allow us to better treat patients with the cardiometabolic syndrome and diabetes in order to reduce CVD morbidity and mortality.

The role of mineralocorticoids in the development of cardiovascular disease (CVD), cardiometabolic syndrome, type 2 diabetes mellitus, chronic kidney disease (CKD), and hypertension is a growing field of interest. Aldosterone, mainly through nongenomic actions that result in proliferation, fibrosis, inflammation, and tissue remodeling, has been linked to CVD and CKD. Increased circulating aldosterone is also associated with insulin resistance and impaired glucose homeostasis that contribute to the development of endothelial dysfunction, atherosclerosis, and kidney disease. Aldosterone-induced oxidative stress and inflammation play a key role in impairing insulin signaling. Mineralocorticoid receptor blockade restores insulin sensitivity, counterbalances the deleterious cardiovascular and renal effects of aldosterone, and emerges as an alternative to improve blockade of the renin-angiotensin-aldosterone system, which potentially could contribute to reduce the burden of CVD and CKD.

The dramatic increase in the prevalence of obesity worldwide represents one of the most important challenges of modern medicine, owing to its myriad related complications-in particular cardiovascular disease, the leading cause of death worldwide. Originating from early studies with Cannabis sativa, the active compound of marijuana, there has been an impressive progress in the knowledge about the endocannabinoid network, leading to the identification of specific pathways that modulate feeding behavior. The effects of endocannabinoids are not limited to the central nervous system, but also include peripheral tissues. Experimental and clinic trials have demonstrated the efficacy of endocannabinoid antagonists in the management of obesity and the cardiometabolic syndrome. Better understanding of the mechanisms underlying obesity will lead to development of more active and specific agents, which surely will enlarge the role of this efficacious alternative for management of obesity.

Diabetes mellitus confers a high risk of cardiovascular morbidity and mortality and requires aggressive management of all cardiovascular risk factors, including diabetic dyslipidemia. Although levels of low-density lipoprotein cholesterol are often normal or only slightly elevated in persons with diabetes, lipid-altering therapy with statins has been shown in large, randomized, controlled trials to decrease the risk of cardiovascular complications in this patient population. A target low-density lipoprotein cholesterol level of