Increase of Homocysteinemia/Hydrogen Sulfide (Hcy/H2S) Ratio Raises Cardiovascular Injuries

Increased Homocysteine Levels (HHcy) is an independent risk factor for atherosclerosis. On the other hand, hydrogen sulfide (H2S) exerts a protection against cardiovascular injuries. On the contrary, accumulating evidences showed that downregulation of defective catabolism of HHcy, with reduced H2S synthesis, is involved in the pathogenesis of a variety of cardiovascular diseases. In that occurrence, the detrimental actions on cardiovascular structures performed by HHcy are added to the negative consequences of reduced H2S (in part unlike each HHcy) on cardiovascular system. Therefore, when the reduced re-methylation pathway of Hcy towards Met (resulting in HHcy) is contemporarily added to the decreased trans-sulfuration pathway (inducing a reduction of H2S synthesis) cardiovascular impairment significantly increases.

Worse Course and Bad Prognosis of COVID-19 in Hyper-Homocysteinemia: Role of Some B-Group Vitamins and of Other Compounds

Background: Increased homocysteine serum levels (HHcy) induce Endothelium Dysfunction (ED), responsible of the activation of some proinflammatory agents (“cytokine storm”), the imbalance between vasodilation and vasoconstriction with vasoconstrictive prevalence, increased oxidative stress and hyper-coagulability. Methods: All these events can worsen the course of COVID-19 in HHcy- patients, favoring the evolution towards vasculitis, thromboembolic complications, multi-organ dysfunction until acute respiratory distress and failure. Results: Therefore, Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) also called COVID-19, elapses more dangerously in patients affected by HHcy and can easily complicate with thromboembolic events. But, some vitamins of B-group and other substances could positively affect both high Hcy levels and thrombotic complications of SARS-CoV-2 happening in lungs and other districts. Conclusions: COVID-19 can have a dangerous evolution and a bad prognosis in patients with HHcy. Concerning this, some compounds seem to exert beneficial effects on HHcy, inflammatory and coagulopathic complications.

A Longitudinal Study on Hematocrit Changes after Glifozins Exposure in Patients with Type 2 Diabetes

Background and Methods: Gliflozins are widely prescribed drugs in patients with type 2 diabetes. We pursue to explain abnormal increments in red cell parameters observed in this population, by means of a longitudinal study in 149 patients with a gliflozins exposure period of 12±6 months. Red cell parameters, HbA1c and other variables were recorded. Results: HbA1c fraction decreased (-0.5±1.3, 95% CI: -0.7 to -0.3, p<0.001), while mean hemoglobin (0.5±0.9, 95% CI: 0.3 to 0.6, P<0.001) and hematocrit (1.6±2.6, 95% CI: 1.2 to 2.0, P<0.001) increased. Mean (SD) hematocrit increased 2.7±1.9 in 112 patients, and decreased -1.7±1.5 in 37 (p<0.001 for subgroup differences). The larger increments in PCV were proportional to higher plasma fraction at baseline (p=0.009). Conclusion: Red cell parameters after gliflozins exposure tend to increase and may reach abnormally high thresholds in some patients with type 2 diabetes.

Galectin-3 in Heart Failure with Preserved Ejection Fraction and Persistent Atrial Fibrillation Versus Sinus Rhythm. Correlation with Left Atrial Volume and N-Terminal Pro B-Type Natriuretic Peptide

Background: Galectin-3 (Gal-3) is considered both a profibrotic biomarker in Heart Failure with preserved Ejection Fraction (HFpEF) and a biomarker of atrial remodeling in Atrial Fibrillation (AF). The Left Atrial Volume Index (LAVI) is an echocardiographic parameter considered an index of left atrial remodeling. Aim of this study was to analyse the relation of Gal-3 levels with both LAVI and N-Terminal Pro B-Type Natriuretic Peptide (NT-proBNP) in patients with HFpEF and Persistent AF (HFpEF-PAF). Methods: Serum Gal-3 and NT-proBNP, along with LAVI were measured. A comparison of such parameters between 49 patients with HFpEF-PAF and 53 patients with HFpEF and sinus rhythm (HEpEF-SR) was made. Results: Galectin-3, NT-proBNP and LAVI were significantly higher in patients with HFpEF-PAF compared to HFpEF-SR (23±7 ng/mL vs 19.5±8.5 ng/mL, p=0.027; 3,406.8±2,321.9 pg/mL vs 1,459.6±1,372 pg/mL, p<0.001; 40.1±11mL/m² vs 28.4±7.7 mL/m², p<0.001, respectively). In HFpEF-PAF, Gal- 3 showed a significant correlation with both NT-proBNP (r=0.40, p=0.0038) and LAVI (r=0.28, p=0.044). We found a significant association between patients with higher levels of Gal-3 >17.8 ng/mL and HFpEF-PAF (p=0.002). Finally, a multivariate logistic regression analysis adjusted for age, sex and traditional clinical AF risk factors showed that Gal-3 >17,8 ng/mL (OR 3.862, 95% CI 1.416 to 10.532, p=0.008) was an independent predictor of PAF. Conclusions: In patients with HFpEF-PAF Gal-3 was higher and related with both NT-proBNP and LAVI. The latter correlation may be relevant because LAVI is considered an index of left atrial remodeling. Moreover, higher levels of Gal-3>17,8 ng/mL were an independent predictor of PAF.

Wearable Devices: A Future Useful Tool for Detection of Silent Ischemia in Patients with Diabetes?

As smartphone health care technology continues to evolve, many wearable devices are equipped with Electrocardiographic (ECG) recording. Recently, studies examining the possibility of various wearable devices for continuous ECG recording showed their ability to detect ST-segment alterations. It is known that in almost a quarter of people with diabetes, the presentation of an acute coronary syndrome may be atypical or even asymptomatic (“silent”), and it has been associated with adverse prognosis. The precise mechanisms behind the lack of pain in patients suffering from silent myocardial ischemia remain unknown. The attractive hypothesis that clinicians could use a wearable ECG recording to detect and treat earlier patients suffering from silent myocardial ischemia might change the adverse prognosis of those patients. However, before their clinical application, several obstacles should be overcome in order the physicians to obtain an additional powerful tool in the fight against coronary artery disease in people with diabetes.

Epigallocatechin Gallate (EGCG) – A Novel Covalent NF- κB Inhibitor: Structural and Molecular Characterization

Tea contains antioxidant catechins thought to exert health-promoting protective effects against conditions involving chronic inflammation, such as cardiovascular diseases. The most abundant catechin in tea is Epigallocatechin Gallate (EGCG), thought to be a key contributor to tea’s health-promoting actions. EGCG exerts protective cardiovascular effects via its antioxidant, antiinflammatory, hypolipidemic, anti-thrombogenic, and anti-hypertensive actions. Because EGCG inhibits the strong proinflammatory gene-inducing transcription factor NF-κB, we analyzed the chemical and molecular details of the mechanism by which EGCG mediates NF-κB inhibition. We quantified and mapped key parameters of its chemical reactivity including its electrophilic Fukui ƒ+ function, in silico covalent binding, and identified its frontier Molecular Orbitals (MOs) and nucleophilic susceptibility. These physical and chemical reactivity parameters revealed that the bond-forming MOs are distributed on the B ring of the EGCG oxidized state with nucleophilic susceptibility, and that this B ring has properties that favor participating in a Cys-alkylating 1,4-addition reaction. Molecular modeling and docking analysis further revealed that EGCG bonds covalently with Cys-38 of NF-κB-p65, and thereby inhibits its DNA binding ability. We also generated a model pharmacophore based on the EGCG-NF-κB complex. We conclude that EGCG covalently binds to NF-κB-p65 and inhibits it by abolishing its DNA binding, by chemical mechanisms that may inform design of EGCG derivatives as novel anti-inflammatory agents.