Coronavirus disease 2019 (COVID-19) is usually more severe and associated with worst outcomes in individuals with pre-existing cardiovascular pathologies, including hypertension or atherothrombosis. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can differentially infect multiple tissues (i.e., lung, vessel, heart, liver) in different stages of disease, and in an age- and sex-dependent manner. In particular, cardiovascular (CV) cells (e.g., endothelial cells, cardiomyocytes) could be directly infected and indirectly disturbed by systemic alterations, leading to hyperinflammatory, apoptotic, thrombotic, and vasoconstrictive responses. Until now, hundreds of clinical trials are testing antivirals and immunomodulators to decrease SARS-CoV-2 infection or related systemic anomalies. However, new therapies targeting the CV system might reduce the severity and lethality of disease. In this line, activation of the non-canonical pathway of the renin-angiotensin-aldosterone system (RAAS) could improve CV homeostasis under COVID-19. In particular, treatments with angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-receptor blockers (ARB) may help to reduce hyperinflammation and viral propagation, while infusion of soluble ACE2 may trap plasma viral particles and increase cardioprotective Ang-(1–9) and Ang-(1–7) peptides. The association of specific ACE2 polymorphisms with increased susceptibility of infection and related CV pathologies suggests potential genetic therapies. Moreover, specific agonists of Ang-(1–7) receptor could counter-regulate the hypertensive, hyperinflammatory, and hypercoagulable responses. Interestingly, sex hormones could also regulate all these RAAS components. Therefore, while waiting for an efficient vaccine, we suggest further investigations on the non-canonical RAAS pathway to reduce cardiovascular damage and mortality in COVID-19 patients.

Uncontrolled type-1 diabetes (T1DM) can lead to dyslipidaemia and albuminuria, which may promote cardiovascular injuries. However, some lipidemic factors could be useful in predicting cardiac dysfunction. Seventy-eight adolescents under insulin treatment due to a 6-year history of T1DM and were retrospectively examined. Glycemia, lipidemia, and albuminuria were measured in addition to development of cardiovascular abnormalities Both girls and boys showed higher HbA1c and fasting blood glucose and 27.1% females and 33.3% males exhibited microalbuminuria though their plasma levels of total cholesterol (TC), triglycerides (TG), and low-density lipoproteins (LDL) and high-density lipoproteins (HDL lipoproteins were in the normal range. They exhibited a preserved systolic function, but 50% of females and 66.6% of males had developed diastolic failures. Interestingly, girls with diastolic dysfunction showed significantly lower concentrations of HDL and higher TC/HDL and TG/HDL ratios. In fact, low HDL levels (OR 0.93; 95% CI 0.88–0.99; p = 0.029) and high TC/HDL (OR 2.55; 95% CI 1.9–5.45; p = 0.016) and TG/HDL (OR 2.74; 95% CI 1.12–6.71; p = 0.028) ratios associated with the development of diastolic complications. The cut-off values for HDL, TC/HDL, and TG/HDL were 49 mg/dL, 3.0 and 1.85, respectively. HDL and TC/HDL and TG/HDL ratios may be useful for predicting diastolic dysfunction in girls with uncontrolled T1DM.

The pathophysiological mechanisms underlying Myocardial Infarction with Non-Obstructive Coronary Artery Disease (MINOCA) are still under debate. Lipoprotein (a) [Lp(a)] has proinflammatory and prothrombotic actions and has been involved in the pathogenesis of atherosclerosis. However, no previous studies have linked Lp(a) levels with the probability of developing MINOCA. Moreover, the relationship between MINOCA and the plasma levels of other proatherogenic and proinflammatory molecules such as Interleukin-18 (IL18) and proprotein convertase subtilisin/kexin type 9 (PCSK9) has not been studied. We conducted a prospective, multicenter study involving 1042 patients with acute myocardial infarction (AMI). Seventy-six patients had no significant coronary lesions. All patients underwent plasma analysis on admission. MINOCA patients were younger (57 (47–68) vs. 61 (52–72) years; p = 0.010), more frequently female (44.7% vs. 21.0%; p < 0.001), and had lower rates of diabetes and of Lp(a) > 60 mg/dL (9.2% vs. 19.8%; p = 0.037) than those with coronary lesions; moreover, High Density Lipoprotein cholesterol (HDL-c) levels were higher in MINOCA patients. The absence of Lp(a) > 60 mg/dL and of diabetes were independent predictors of MINOCA, as well as female sex, high HDL-c levels, and younger age. IL-18 and PCSK9 levels were not predictors of MINOCA. During a follow-up of 5.23 (2.89, 7.37) years, the independent predictors of the primary outcome (acute ischemic events or death) in the whole sample were Lp(a) > 60 mg/dL, older age, low estimated Glomerular Filtration rate (eGFR), hypertension, previous heart failure (HF), coronary artery bypass graft, use of insulin, and no therapy with acetylsalicylic acid. In conclusion, in AMI patients, the absence of high Lp(a) levels, as well high HDL-c levels, were independent predictors of the inexistence of coronary artery disease. High Lp (a) levels were also an independent predictor of ischemic events or death.

Obesity is becoming a pandemic and percutaneous electrical stimulation (PENS) of dermatome T6 has been demonstrated to reduce stomach motility and appetite, allowing greater weight loss than isolated hypocaloric diets. However, modulation of intestinal microbiota could improve this effect and control cardiovascular risk factors. Our objective was to test whether addition of probiotics could improve weight loss and cardiovascular risk factors in obese subjects after PENS and a hypocaloric diet. A pilot prospective study was performed in patients (n = 20) with a body mass index (BMI) > 30 kg/m2. Half of them underwent ten weeks of PENS in conjunction with a hypocaloric diet (PENS-Diet), and the other half was treated with a PENS-Diet plus multistrain probiotics (L. plantarum LP115, B. brevis B3, and L. acidophilus LA14) administration. Fecal samples were obtained before and after interventions. The weight loss and changes in blood pressure, glycemic and lipid profile, and in gut microbiota were investigated. Weight loss was significantly higher (16.2 vs. 11.1 kg, p = 0.022), whereas glycated hemoglobin and triglycerides were lower (−0.46 vs. −0.05%, p = 0.032, and −47.0 vs. −8.5 mg/dL, p = 0.002, respectively) in patients receiving PENS-Diet + probiotics compared with those with a PENS-Diet. Moreover, an enrichment of anti-obesogenic bacteria, including Bifidobacterium spp, Akkermansia spp, Prevotella spp, and the attenuation of the Firmicutes/Bacteroidetes ratio were noted in fecal samples after probiotics administration. In obese patients, the addition of probiotics to a PENS intervention under a hypocaloric diet could further improve weight loss and glycemic and lipid profile in parallel to the amelioration of gut dysbiosis.

BackgroundIn the cardiovascular (CV) system, overactivation of the angiotensin converting enzyme (ACE) may trigger deleterious responses derived from angiotensin (Ang)-II, which can be attenuated by stimulation of ACE2 and subsequent Ang-(1-7) metabolite. However, ACE2 exhibits a high degree of genetic polymorphism that may affect its structure and stability, interfering with these cardioprotective actions. The aim of this study was to analyse the relationship of ACE2 polymorphisms with cardiovascular risk factors in children.MethodologyFive ACE2-single nucleotide polymorphisms (SNP), rs4646188, rs2158083, rs233575, rs879922, and rs2074192, previously related to CV risk factors, were analyzed in a representative sample of 12–16-year-old children and tested for their potential association with anthropometric parameters, insulin levels and the lipid profile.ResultsGirls (N = 461) exhibited lower rates of overweight, obesity, blood pressure, and glycemia than boys (N = 412), though increased plasma lipids. The triglycerides (TG)/HDL-C ratio was, however, lower in females. Interestingly, only in girls, the occurrence of overweight/obesity was associated with the SNPs rs879922 [OR 1.67 (1.02–2.75)], rs233575 [OR 1.98 (1.21- 3.22)] and rs2158083 [OR 1.67 (1.04–2.68)]. Also, TG levels were linked to the rs879922, rs233575, and rs2158083 SNPs, and the TG/HDL-C ratio was associated with rs879922 and rs233575. Levels of TC and LDL-C were associated with rs2074192 and rs2158083. Furthermore, the established cut-off level for TG ≥ 90 mg/dL was related to rs879922 [OR 1.78 (1.06–2.96)], rs2158083 [OR 1.75 (1.08–2.82)], and rs233575 [OR 1.62 (1.00–2.61)]. The cut-off level for TC ≥ 170 mg/dL was associated with rs2074192 OR 1.54 (1.04–2.28) and rs2158083 [OR 1.53 (1.04–2.25)]. Additionally, the haplotype (C-G-C) derived from rs879922-rs2158083-rs233575 was related to higher prevalence of overweight/obesity and TG elevation.ConclusionThe expression and activity of ACE2 may be essential for CV homeostasis. Interestingly, the ACE2-SNPs rs879922, rs233575, rs2158083 and rs2074192, and the haplotype (C-G-C) of the three former could induce vulnerability to obesity and hyperlipidemia in women. Thus, these SNPs might be used as predictive biomarkers for CV diseases and as molecular targets for CV therapy.

Type-2 diabetes (T2DM) and arterial hypertension (HTN) are major risk factors for heart failure. Importantly, these pathologies could induce synergetic alterations in the heart, and the discovery of key common molecular signaling may suggest new targets for therapy. Intraoperative cardiac biopsies were obtained from patients with coronary heart disease and preserved systolic function, with or without HTN and/or T2DM, who underwent coronary artery bypass grafting (CABG). Control (n = 5), HTN (n = 7), and HTN + T2DM (n = 7) samples were analysed by proteomics and bioinformatics. Additionally, cultured rat cardiomyocytes were used for the analysis (protein level and activation, mRNA expression, and bioenergetic performance) of key molecular mediators under stimulation of main components of HTN and T2DM (high glucose and/or fatty acids and angiotensin-II). As results, in cardiac biopsies, we found significant alterations of 677 proteins and after filtering for non-cardiac factors, 529 and 41 were changed in HTN-T2DM and in HTN subjects, respectively, against the control. Interestingly, 81% of proteins in HTN-T2DM were distinct from HTN, while 95% from HTN were common with HTN-T2DM. In addition, 78 factors were differentially expressed in HTN-T2DM against HTN, predominantly downregulated proteins of mitochondrial respiration and lipid oxidation. Bioinformatic analyses suggested the implication of mTOR signaling and reduction of AMPK and PPARα activation, and regulation of PGC1α, fatty acid oxidation, and oxidative phosphorylation. In cultured cardiomyocytes, an excess of the palmitate activated mTORC1 complex and subsequent attenuation of PGC1α-PPARα transcription of β-oxidation and mitochondrial electron chain factors affect mitochondrial/glycolytic ATP synthesis. Silencing of PGC1α further reduced total ATP and both mitochondrial and glycolytic ATP. Thus, the coexistence of HTN and T2DM induced higher alterations in cardiac proteins than HTN. HTN-T2DM subjects exhibited a marked downregulation of mitochondrial respiration and lipid metabolism and the mTORC1-PGC1α-PPARα axis might account as a target for therapeutical strategies.

Background: Type-2 diabetes (T2DM) and arterial hypertension (HTN) are major risk factors for heart failure. Importantly, these pathologies could induce synergetic alterations in the heart, and the discovery of key molecular signaling may suggest new targets for therapy. Methods and Results:: Intraoperative cardiac biopsies were obtained from patients with or without HTN and/or T2DM. Control (n=5), HTN (n=7) and HTN+T2DM (n=7) samples were analyzed by proteomics and bioinformatics. Cultured cardiomyocytes were used for further in vitro studies. In cardiac biopsies from patients with cardiopathy but preserved systolic function we found significant alterations of 677 proteins. After filtered out non-cardiac factors, 529 and 41 were changed in HTN-T2DM and in HTN subjects, respectively, against control. Interestingly, 81% of proteins in HTN-T2DM were distinct from HTN, while 95% from HTN were common with HTN-T2DM. In addition, 78 factors were differentially expressed in HTN-T2DM against HTN, predominantly downregulated proteins of mitochondrial respiration and lipid oxidation. Bioinformatic analyses suggested implication of mTOR signaling and reduction of AMPK and PPARα activation, and regulation of PGC1α, fatty acid oxidation, and oxidative phosphorylation. In cultured cardiomyocytes, an excess of palmitate activated mTOR-C1 complex and subsequent attenuation of PGC1α-PPARα transcription of b-oxidation and mitochondrial electron chain factors, affecting the mitochondrial/glycolytic ATP synthesis. Conclusions: The coexistence of HTN and T2DM induced higher alterations in cardiac proteins than HTN. HTN-T2DM subjects exhibited a dramatic downregulation of mitochondrial respiration and lipid metabolism. The mTOR-C1-PGC1α-PPARα axis might account as a target for future therapies.

INTRODUCTIONFicolins belong to the lectins family. They activate the complement system as an effect in defence of the carrier, and play a very important role in the innate immunity.Three kinds of human Ficolins were earlier described: L, H and M ones. The theory of molecular dissemination is the basis of the behavior's approach from these proteins that can be found in cerebrospinal fluid (CSF).OBJECTIVETo demonstrate through the dynamic of the dissemination from blood to CSF and its concentrations the different ways of molecular adding towards CSF and its action in this biological liquid.METHODS80 serum and CSF paired samples were obtained from control persons without neuroinflammation process and without oligoclonal IgG bands. M ficolin and albumin were quantified by ELISA and by an immunoturbidimetric analysis. Q albumin=CSF albumin/serum albumin and Q, M Ficolin=CSF M Ficolin/serum M ficolin was calculated.To calculate the different aggregation forms were determinate the inflection points of the frequency distribution of M ficolin vs. Q M Ficolin taking into account that the more complex structure should diffuse more than a most simple one.RESULTSSerum and CSF M ficolin did not follow a normal distribution according to Kolmogorov‐Smirnov test. Mean values of M ficolin in serum was higher than its mean content in CSF. CSF M ficolin concentration increased with the increase of Q albumin. M ficolin is not a brain‐derived protein. Three inflection points was determined. (Table 1 and figure 1). G‐1, G‐2, G‐3 described the subpopulation of samples diffusion limited by their molecular weight and its aggregation structure.CONCLUSIONM ficolin is a predominant blood‐derived protein and the diffusion from blood to CSF indicates three aggregation forms.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.