Nitric oxide and fibrinogen in patients with subclinical hypothyroidism and their possible relation to cardiovascular damage

Endothelial dysfunction as well as hypercoagulability have been described as the initial triggers of atherosclerosis and cardiovascular damage and have been associated with subclinical hypothyroidism (SHC). The aim of this research was to determine the concentration of nitric oxide (NO), fibrinogen and circulating lipids in patients with subclinical hypothyroidism and to correlate these variables with thyrotropin (TSH) concentration to establish their possible association with the development of cardiovascular damage. A descriptive, cross-sectional, correlational study was conducted at the IESS Hospital in Riobamba, Ecuador, in the period from January 2019 to September 2021. Ninety-five subjects were studied (65 patients with CAH and 30 controls). The concentration of total cholesterol, triglycerides, HDL cholesterol and LDL cholesterol, TSH, free thyroxine, ON and fibrinogen were determined. Results: We found a decrease in the concentration of ON (p<0.001), accompanied by an increase in the concentration of total cholesterol (p<0.0001), LDL cholesterol (p<0.01) and fibrinogen (p<0.0001) in patients with CAH vs. controls. A negative correlation (p<0.0001; r= -0.5020) was observed between TSH and ON and a positive correlation (p<0.0001; r= 5412) between TSH and plasma fibrinogen in patients with CAH. Conclusion: patients with CAH showed a decrease in serum ON levels and an elevation in plasma fibrinogen concentration. Both measurements correlated significantly with TSH concentration. These parameters associated with an increase in total cholesterol and LDL cholesterol could favor vascular dysfunction, the development of atherosclerosis and consequent cardiovascular damage.

Phosphorus Supplementation Mitigates Perivascular Adipose Inflammation–Induced Cardiovascular Consequences in Early Metabolic Impairment

Background The complexity of the interaction between metabolic dysfunction and cardiovascular complications has long been recognized to extend beyond simple perturbations of blood glucose levels. Yet, structured interventions targeting the root pathologies are not forthcoming. Growing evidence implicates the inflammatory changes occurring in perivascular adipose tissue (PVAT) as early instigators of cardiovascular deterioration. Methods and Results We used a nonobese prediabetic rat model with localized PVAT inflammation induced by hypercaloric diet feeding, which dilutes inorganic phosphorus (Pi) to energy ratio by 50%, to investigate whether Pi supplementation ameliorates the early metabolic impairment. A 12‐week Pi supplementation at concentrations equivalent to and twice as much as that in the control diet was performed. The localized PVAT inflammation was reversed in a dose‐dependent manner. The increased expression of UCP1 (uncoupling protein1), HIF‐1α (hypoxia inducible factor‐1α), and IL‐1β (interleukin‐1β), representing the hallmark of PVAT inflammation in this rat model, were reversed, with normalization of PVAT macrophage polarization. Pi supplementation restored the metabolic efficiency consistent with its putative role as an UCP1 inhibitor. Alongside, parasympathetic autonomic and cerebrovascular dysfunction function observed in the prediabetic model was reversed, together with the mitigation of multiple molecular and histological cardiovascular damage markers. Significantly, a Pi‐deficient control diet neither induced PVAT inflammation nor cardiovascular dysfunction, whereas Pi reinstatement in the diet after a 10‐week exposure to a hypercaloric low‐Pi diet ameliorated the dysfunction. Conclusions Our present results propose Pi supplementation as a simple intervention to reverse PVAT inflammation and its early cardiovascular consequences, possibly through the interference with hypercaloric‐induced increase in UCP1 expression/activity.

Pharmacological properties of selenium and its preparations: from antioxidant to neuroprotector

Selenium is an essential component of more than two dozen enzymes and other selenoproteins that play critical roles in reproduction, DNA synthesis, thyroid hormone metabolism, and protection from oxidative damage and infection. Selenium has a protective action against some forms of cancer and cardiovascular diseases, modulates levels of inflammatory mediators, promotes to maintain bone homeostasis and protects against bone loss. Selenium significance as a cardioprotective agent may be associated not only with its antioxidant properties, but also with its ability to prevent inflammation, autophagy, as well as the intrinsic and extrinsic apoptosis pathways. Signaling pathways, such as p-AMPK, PARP, Nrf2, STAT, are involved in the protective effects of selenium. Selenium protects against cardiovascular damage by increasing the survival rate of cardiomyocytes, including a mitochondria-dependent pathway and autophagy through peroxisome proliferator-activated receptors. Research demonstrating neuroprotective and cardioprotective effects of selenium preparations – selenoline, selenocysteine and selenomethionine – is growing at a rapid rate. It has been established that these compounds are able to normalize the levels of heat shock proteins (HSP70), which limit the cytotoxic effects of free radicals, produce energotropic action, prevent a decrease in the membrane mitochondria charge, and the opening of the mitochondrial pore. Also regulate the expression of transmembrane factors NF-kB, c-fos, which is associated with their main biological function of chaperone proteins, providing protection of neurons from damage. In this review, we want to emphasize pharmacological role of Selenium and its derivatives on human health is very complex and has yet to be fully understood.

466 The role of pulmonary act in the patient with SARS-CoV-2 infection

Already from the first data in China in early 2020 it emerged that patients with cardiovascular comorbidities had an increased risk of contracting SARS-CoV-2 infection and a more unfavourable clinical course. From March to May 2020, 85 patients affected by COVID-19 were enrolled, hospitalized at the Great Metropolitan Hospital of Reggio Calabria. The mean age was 63.6 ± 16.5 years. All patients underwent anamnesis, clinical evaluation, chest CT, ECG and measurement of markers of cardiovascular damage (Troponin I, CK-MB, LDH, D-dimer, BNP) and of inflammation (PCR, IL-6, and PCT). Thirty-one patients underwent echocardiography to look for signs of left ventricular dysfunction and/or repercussions of lung disease on the right sections. In particular, we evaluated parietal dimensions and thicknesses, biventricular function and transvalvular tricuspid and pulmonary flows and correlated the data obtained with ECG, radiological, clinical, and biohumoral parameters. The aim of our study was to evaluate the prognostic impact of cardiovascular involvement in COVID-19, investigating the effect of cardiovascular risk factors, levels of cardiovascular damage markers and newly emerging ECG and echocardiographic changes on a composite primary endpoint, consisting of the combination of exitus and the need for intensive care (ICU). For this purpose, the enrolled patients were divided into two subpopulations: those with better prognosis and those with poorer prognosis (ICU/exitus). We then analysed the reciprocal correlation of each of the investigated parameters and searched for the presence of echocardiographic signs of repercussion on the right sections of the pulmonary pathology. Among the patients with the poorest prognosis, 81.2% were hypertensive, 12.5% diabetic, 25% dyslipidaemic. Comparing the two subpopulations analysed, it emerged that patients with the worst prognosis were known hypertensive (P 0.02). Longer QTc intervals were associated with higher levels of CRP (P &lt; 0.0001) and PCT (P 0.005). All markers of cardiovascular damage had significantly higher values in the most critically ill patients (P 0.001 for d-dimer, P &lt; 0.001 for baseline and peak Troponin, P 0.001 for CK-MB, P 0.007 for BNP) and similar behaviour had indices of inflammation (P &lt; 0.001 for PCR and IL-6). Patients with poorer prognosis had significantly lower lung AcT values ( P 0.002), which correlated with higher d-dimer levels (P 0.01) and more complicated hospital stays (P 0.02). There were no statistically significant differences between PAPs, right ventricular size, TAPSE, and pulmonary trunk diameter in the two subpopulations. Larger right ventricular diameters were associated with more dilated lung trunks (P 0.009) and higher IL-6 levels (P 0.004). The most interesting data of our study is the behaviour of pulmonary AcT: lower values of AcT were associated with higher levels of d-dimer, as an expression of a greater pulmonary microthrombotic burden, and a poorer prognosis, in the presence of PAPs basically normal. The dynamic analysis of this parameter, which is easy to calculate in the patient's bed, can play a crucial role in the instrumental follow-up of patients hospitalized for SARS-CoV-2 infection.

Roles of NAD(P)H:quinone Oxidoreductase 1 in Diverse Diseases

NAD(P)H:quinone oxidoreductase (NQO) is an antioxidant flavoprotein that catalyzes the reduction of highly reactive quinone metabolites by employing NAD(P)H as an electron donor. There are two NQO enzymes—NQO1 and NQO2—in mammalian systems. In particular, NQO1 exerts many biological activities, including antioxidant activities, anti-inflammatory effects, and interactions with tumor suppressors. Moreover, several recent studies have revealed the promising roles of NQO1 in protecting against cardiovascular damage and related diseases, such as dyslipidemia, atherosclerosis, insulin resistance, and metabolic syndrome. In this review, we discuss recent developments in the molecular regulation and biochemical properties of NQO1, and describe the potential beneficial roles of NQO1 in diseases associated with oxidative stress.

Serum apolipoprotein A-I depletion is causative to silica nanoparticles–induced cardiovascular damage

The rapid development of nanotechnology has greatly benefited modern science and engineering and also led to an increased environmental exposure to nanoparticles (NPs). While recent research has established a correlation between the exposure of NPs and cardiovascular diseases, the intrinsic mechanisms of such a connection remain unclear. Inhaled NPs can penetrate the air–blood barrier from the lung to systemic circulation, thereby intruding the cardiovascular system and generating cardiotoxic effects. In this study, on-site cardiovascular damage was observed in mice upon respiratory exposure of silica nanoparticles (SiNPs), and the corresponding mechanism was investigated by focusing on the interaction of SiNPs and their encountered biomacromolecules en route. SiNPs were found to collect a significant amount of apolipoprotein A-I (Apo A-I) from the blood, in particular when the SiNPs were preadsorbed with pulmonary surfactants. While the adsorbed Apo A-I ameliorated the cytotoxic and proinflammatory effects of SiNPs, the protein was eliminated from the blood upon clearance of the NPs. However, supplementation of Apo A-I mimic peptide mitigated the atherosclerotic lesion induced by SiNPs. In addition, we found a further declined plasma Apo A-I level in clinical silicosis patients than coronary heart disease patients, suggesting clearance of SiNPs sequestered Apo A-I to compromise the coronal protein’s regular biological functions. Together, this study has provided evidence that the protein corona of SiNPs acquired in the blood depletes Apo A-I, a biomarker for prediction of cardiovascular diseases, which gives rise to unexpected toxic effects of the nanoparticles.

Prolonged Administration of Rudgea viburnoides (Cham.) Benth. Prevents Impairment of Redox Status, Renal Dysfunction, and Cardiovascular Damage in 2K1C-Hypertensive Rats by Inhibiting ACE Activity and NO-GMPC Pathway Activation

Rudgea viburnoides is widely found in the Brazilian Cerrado, and commonly used in Brazilian folk medicine. In this study, we evaluated the effects of prolonged administration of the aqueous extract from R. viburnoides leaves (AERV) on impaired redox status, renal dysfunction, and cardiovascular damage in 2K1C hypertensive rats, as well as its chemical composition by LC-DAD-MS. Renal hypertension (two kidney, one-clip model) was surgically induced in male Wistar rats and AERV (30, 100 and 300 mg/kg) was administered orally five weeks after surgery for 28 days. Renal function was assessed and urinary electrolytes, pH, and density were measured. Electrocardiography, blood pressure and heart rate were recorded. Cardiac and mesenteric vascular beds were isolated for cardiac morphometry and evaluation of vascular reactivity, and aortic rings were also isolated for measurement of cyclic guanosine monophosphate levels, and the redox status was assessed. Prolonged treatment with AERV preserved urine excretion and electrolyte levels (Na+, K+, Ca2+ and Cl−), reversed electrocardiographic changes, left ventricular hypertrophy and changes in vascular reactivity induced by hypertension, and reduced blood pressure and heart rate. This effect was associated with a positive modulation of tissue redox state, activation of the NO/cGMP pathway, and inhibition of the angiotensin-converting enzyme. Glycosylated iridoids, chlorogenic acids, glycosylated triterpenes, O-glycosylated flavonols, and triterpenoid saponins were annotated. AERV showed no acute toxicity in female Wistar rats. Therefore, AERV treatment reduced the progression of cardiorenal disease in 2K1C hypertensive rats, which can be involved with an important attenuation of oxidative stress, angiotensin-converting enzyme inhibition, and activation of the NO/cGMP pathway.

Sudden infant death syndrome: Melatonin, serotonin, and CD34 factor as possible diagnostic markers and prophylactic targets

Sudden infant death syndrome (SIDS) is one of the primary causes of death of infants in the first year of life. According to the WHO’s data, the global infant mortality rate is 0.64–2 per 1,000 live-born children. Molecular and cellular aspects of SIDS development have not been identified so far. The purpose of this paper is to verify and analyze the expression of melatonin 1 and 2 receptors, serotonin (as a melatonin precursor), and CD34 molecules (as hematopoietic and endothelial markers of cardiovascular damage) in the medulla, heart, and aorta in infants who died from SIDS. An immunohistochemical method was used to investigate samples of medulla, heart, and aorta tissues of infants 3 to 9 months of age who died from SIDS. The control group included children who died from accidents. It has been shown that the expression of melatonin receptors as well as serotonin and CD34 angiogenesis markers in tissues of the medulla, heart, and aorta of infants who died from SIDS is statistically lower as compared with their expression in the same tissues in children who died from accidents. The obtained data help to clarify in detail the role of melatonin and such signaling molecules as serotonin and CD34 in SIDS pathogenesis, which can open new prospects for devising novel methods for predictive diagnosis of development and targeted prophylaxis of SIDS.