Background:
Sodium–glucose cotransporter 2 (SGLT2), also known as solute carrier family 5 member 2 (SLC5A2), is a promising target for a new class of drugs primarily established as kidney-targeting, ...effective glucose-lowering agents used in diabetes mellitus (DM) patients. Increasing evidence indicates that besides renal effects, SGLT2 inhibitors (SGLT2i) have also a systemic impact via indirectly targeting the heart and other tissues. Our hypothesis states that the pleiotropic effects of SGLT2i are associated with their binding force, location of targets in the SGLT2 networks, targets involvement in signaling pathways, and their tissue-specific expression.
Methods:
Thus, to investigate differences in SGLT2i impact on human organisms, we re-created the SGLT2 interaction network incorporating its inhibitors and metformin and analyzed its tissue-specific expression using publicly available datasets. We analyzed it in the context of the so-called key terms ( autophagy, oxidative stress, aging, senescence, inflammation, AMPK pathways, and mTOR pathways) which seem to be crucial to elucidating the SGLT2 role in a variety of clinical manifestations.
Results:
Analysis of SGLT2 and its network components’ expression confidence identified selected organs in the following order: kidney, liver, adipose tissue, blood, heart, muscle, intestine, brain, and artery according to the TISSUES database. Drug repurposing analysis of known SGLT2i pointed out the influence of SGLT1 regulators on the heart and intestine tissue. Additionally, dapagliflozin seems to also have a stronger impact on brain tissue through the regulation of SGLT3 and SLC5A11. The shortest path analysis identified interaction SIRT1-SGLT2 among the top five interactions across six from seven analyzed networks associated with the key terms. Other top first-level SGLT2 interactors associated with key terms were not only ADIPOQ, INS, GLUT4, ACE, and GLUT1 but also less recognized ILK and ADCY7. Among other interactors which appeared in multiple shortest-path analyses were GPT, COG2, and MGAM. Enrichment analysis of SGLT2 network components showed the highest overrepresentation of hypertensive disease, DM-related diseases for both levels of SGLT2 interactors. Additionally, for the extended SGLT2 network, we observed enrichment in obesity (including SGLT1), cancer-related terms, neuroactive ligand–receptor interaction, and neutrophil-mediated immunity.
Conclusion:
This study provides comprehensive and ranked information about the SGLT2 interaction network in the context of tissue expression and can help to predict the clinical effects of the SGLT2i.
Background
COVID‐19 is generating clinical challenges, lifestyle changes, economic consequences. The pandemic imposes to familiarize with concepts as prevention, vulnerability and resilience.
Methods
...We analysed and reviewed the most relevant papers in the MEDLINE database on syndemic, noncommunicable diseases, pandemic, climate changes, pollution, resilience, vulnerability, health costs, COVID‐19.
Results
We discuss that comprehensive strategies must face multifactorial consequences since the pandemic becomes syndemic due to interactions with noncommunicable diseases, climate changes and iniquities. The lockdown experience, on the other hand, demonstrates that it is rapidly possible to reverse epidemiologic trends and to reduce pollution. The worst outcome is evident in eight highly industrialized nations, where 12% of the world population experienced about one‐third of all COVID‐19‐deaths worldwide. Thus, a great economic power has not been fully protective, and a change of policy is obviously needed to avoid irreversible consequences.
Conclusions
We are accumulating unhealthy populations living in unhealthy environments and generating unhealthy offspring. The winning policy should tackle structural inequities through a syndemic approach, to protect vulnerable populations from present and future harms.
COVID-19 challenge for modern medicine Dzieciatkowski, Tomasz; Szarpak, Lukasz; Filipiak, Krzysztof J ...
Cardiology Journal,
05/2020, Volume:
27, Issue:
2
Journal Article
Peer reviewed
Open access
Coronaviruses cause disease in animals and people around the world. Human coronaviruses (HCoV) are mainly known to cause infections of the upper and lower respiratory tract but the symptoms may also ...involve the nervous and digestive systems. Since the beginning of December 2019, there has been an epidemic of SARS-CoV-2, which was originally referred to as 2019-nCoV. The most common symptoms are fever and cough, fatigue, sputum production, dyspnea, myalgia, arthralgia or sore throat, headache, nausea, vomiting or diarrhea (30%). The best prevention is to avoid exposure. In addition, contact per-sons should be subjected to mandatory quarantine. COVID-19 patients should be treated in specialist centers. A significant number of patients with pneumonia require passive oxygen therapy. Non-invasive ventilation and high-flow nasal oxygen therapy can be applied in mild and moderate non-hypercapnia cases. A lung-saving ventilation strategy must be implemented in acute respiratory distress syndrome and mechanically ventilated patients. Extracorporeal membrane oxygenation is a highly specialized method, available only in selected centers and not applicable to a significant number of cases. Specific pharmacological treatment for COVID-19 is not currently available. Modern medicine is gearing up to fight the new coronavirus pandemic. The key is a holistic approach to the patient including, primar-ily, the use of personal protective equipment to reduce the risk of further virus transmission, as well as patient management, which consists in both quarantine and, in the absence of specific pharmacological therapy, symptomatic treatment.
The vegan diet, often known as a plant-rich diet, consists primarily of plant-based meals. This dietary approach may be beneficial to one's health and the environment and is valuable to the immune ...system. Plants provide vitamins, minerals, phytochemicals, and antioxidants, components that promote cell survival and immune function, allowing its defensive mechanisms to work effectively. The term "vegan diet" comprises a range of eating patterns that prioritize nutrient-rich foods such as fruits and vegetables, legumes, whole grains, nuts, and seeds. In comparison to omnivorous diets, which are often lower in such products, the vegan diet has been favorably connected with changes in cardiovascular disease (CVD) risk markers such as reduced body mass index (BMI) values, total serum cholesterol, serum glucose, inflammation, and blood pressure. Reduced intake of low-density lipoprotein (LDL), saturated fat, processed meat, and greater consumption of fiber and phytonutrients may improve cardiovascular health. However, vegans have much smaller amounts of nutrients such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), selenium, zinc, iodine, and vitamin B12, compared to non-vegans, which may lead to detrimental cardiovascular effects. This review aims to present the effect of plant-based diets (PBDs), specifically vegan diets, on the cardiovascular system.
Lipoprotein apheresis (LA) is a therapeutic option for hyperlipoproteinemia(a) (hyper-Lp(a)) and atherosclerotic cardiovascular disease (ASCVD). LA improves blood rheology, reduces oxidative stress ...parameters and improves endothelial function. The underlying molecular mechanisms of LA beneficial effects are unknown, but it has been suggested that LA exhibits multiple activities beyond simply removing lipoproteins. We hypothesized that LA removes not only lipoproteins, but also extracellular vesicles (EVs). To test this hypothesis, we performed a prospective study in 22 patients undergoing LA for hyper-Lp(a) and ASCVD. Different EVs subtypes were measured before and directly after LA, and after 7 days. We used calibrated flow cytometry to detect total particle concentration (diameter > ~ 100 nm), total lipoproteins concentration (diameter > 200 nm, RI > 1.51), total EV concentration (diameter > 200 nm, RI < 1.41), concentrations of EVs derived from erythrocytes (CD235a+; diameter > 200 nm, RI < 1.41), leukocytes (CD45+; diameter > 200 nm, RI < 1.41) and platelets (CD61+, PEVs; diameter > 200 nm, RI < 1.41). LA reduced the concentrations of all investigated EVs subtypes and lipoproteins. Lp(a) concentration was lowered by 64.5% (58% - 71%); p < 0.001. Plasma concentrations of EVs > 200 nm in diameter derived from platelets (CD61 +), leukocytes (CD45+) and erythrocytes (CD235a+) decreased after single LA procedure by 42.7% (12.8-54.7); p = 0.005, 42.6% (29.7-54.1); p = 0.030 and 26.7% (1.0-62.7); p = 0.018, respectively, compared to baseline. All EV subtypes returned to the baseline concentrations in blood plasma after 7 days. To conclude, LA removes not only Lp(a), but also cell-derived EVs, which may contribute to LA beneficial effects.
Abstract Circulating cell-derived microvesicles (MV) represent a subject of increasing interest in recent years as potential effectors in thrombosis, inflammation and vascular injury. Although ...several studies demonstrated an association between MV plasma concentrations and clinical manifestations of atherosclerosis as well as a clear effect of cardiovascular pharmacotherapy on MV formation pattern, the application of this promising biomarkers in clinical cardiology has been hindered so far due to heterogeneity of the hitherto studies employing non-standardized methodologies. Recently great progresses have been done and international initiatives were started to unify the pre-analytical and analytical procedures, improve the comparison of measurements between the laboratories and increase detector sensitivity of flow cytometry — a golden standard for MV assessment. Likewise, the concept of a “therapeutic window” of P2Y12 inhibitor therapy was introduced, as the prognostic significance of bleeding consequences is equally important with that of ischemic events, particularly with the expanding use of more potent P2Y12 inhibitors. In this review we summarize currently available studies on circulating MV in terms of cardiovascular diagnosis, risk stratification and influence of antiplatelet agents on the MV release to postulate possible future role of MV as supplementary biomarker in monitoring of individual response to antiplatelet therapy. Methodological pitfalls faced in the previous studies and obstacles that need to be addressed before further trials and translation of MV-based assays into clinical practice were defined.
This randomized controlled multicenter trial evaluated coenzyme Q10 (CoQ10) as adjunctive treatment in chronic heart failure (HF).
CoQ10 is an essential cofactor for energy production and is also a ...powerful antioxidant. A low level of myocardial CoQ10 is related to the severity of HF. Previous randomized controlled trials of CoQ10 in HF were underpowered to address major clinical endpoints.
Patients with moderate to severe HF were randomly assigned in a 2-year prospective trial to either CoQ10 100 mg 3 times daily or placebo, in addition to standard therapy. The primary short-term endpoints at 16 weeks were changes in New York Heart Association (NYHA) functional classification, 6-min walk test, and levels of N-terminal pro-B type natriuretic peptide. The primary long-term endpoint at 2 years was composite major adverse cardiovascular events as determined by a time to first event analysis.
A total of 420 patients were enrolled. There were no significant changes in short-term endpoints. The primary long-term endpoint was reached by 15% of the patients in the CoQ10 group versus 26% in the placebo group (hazard ratio: 0.50; 95% confidence interval: 0.32 to 0.80; p = 0.003) by intention-to-treat analysis. The following secondary endpoints were significantly lower in the CoQ10 group compared with the placebo group: cardiovascular mortality (9% vs. 16%, p = 0.026), all-cause mortality (10% vs. 18%, p = 0.018), and incidence of hospital stays for HF (p = 0.033). In addition, a significant improvement of NYHA class was found in the CoQ10 group after 2 years (p = 0.028).
Long-term CoQ10 treatment of patients with chronic HF is safe, improves symptoms, and reduces major adverse cardiovascular events. (Coenzyme Q10 as adjunctive treatment of chronic heart failure: a randomised, double-blind, multicentre trial with focus on SYMptoms, BIomarker status Brain-Natriuretic Peptide (BNP), and long-term Outcome hospitalisations/mortality; ISRCTN94506234).
Background
Platelet P2Y12 antagonist ticagrelor reduces mortality after acute myocardial infarction (AMI) compared to clopidogrel, but the underlying mechanism is unknown. Because activated ...platelets, leukocytes, and endothelial cells release proinflammatory and prothrombotic extracellular vesicles (EVs), we hypothesized that the release of EVs is more efficiently inhibited by ticagrelor compared to clopidogrel.
Objectives
We compared EV concentrations and EV procoagulant activity in plasma of patients after AMI treated with ticagrelor or clopidogrel.
Methods
After percutaneous coronary intervention, 60 patients with first AMI were randomized to ticagrelor or clopidogrel. Flow cytometry was used to determine concentrations of EVs from activated platelets (CD61+, CD62p+), fibrinogen+, phosphatidylserine (PS+), leukocytes (CD45+), endothelial cells (CD31+, 146+), and erythrocytes (CD235a+) in plasma at randomization, after 72 hours and 6 months of treatment. A fibrin generation test was used to determine EV procoagulant activity.
Results
Concentrations of platelet, fibrinogen+, PS+, leukocyte, and erythrocyte EVs increased 6 months after AMI compared to the acute phase of AMI (P ≤ .03). Concentrations of platelet EVs were lower on ticagrelor compared to clopidogrel after 6 months (P = .03). Concentrations of fibrinogen+, PS+, and leukocyte EVs were lower on ticagrelor compared to clopidogrel both after 72 hours and 6 months (P ≤ .03). Concentrations of endothelial EVs and EV procoagulant activity did not differ between patient groups and over time (P ≥ .17).
Conclusions
Ticagrelor attenuates the increase of EV concentrations in plasma after acute myocardial infarction compared to clopidogrel. The ongoing release of EVs despite antiplatelet therapy might explain recurrent thrombotic events after AMI and worse clinical outcomes on clopidogrel compared to ticagrelor.
Atherosclerosis is a process whose onset can be observed even in the foetal period. A number of risk factors, such as hyperlipidaemia, hyperhomocysteinaemia, arterial hypertension, hyperuricaemia, ...smoking, metabolic syndrome, hypertriglyceridaemia, and diabetes, accelerate the progression of atherosclerotic lesions leading to the development of atherosclerotic cardiovascular disease (ASCVD) 1.
Atherosclerotic cardiovascular disease is defined as coronary artery disease (CAD), cerebrovascular disease, or peripheral arterial disease of atherosclerotic origin. This disease represents the number one cause of morbidity and mortality worldwide. The number of patients with cardiovascular diseases in the world in 2019 was 523 million, while the number of deaths due to them reached 18.6 million 2.
Atherosclerosis and its complications, including acute coronary syndromes, are the major cause of death worldwide. The two most important pathophysiological mechanisms underlying atherosclerosis ...include increased platelet activation and increased low-density lipoproteins (LDL) concentration. In contrast to LDL, oxidized (ox)-LDL have direct pro-thrombotic properties by functional interactions with platelets, leading to platelet activation and favoring thrombus formation. In this review, we summarize the currently available evidence on the interactions between LDL-cholesterol and platelets, which are based on (i) the presence of ox-LDL-binding sites on platelets, (ii) generation of ox-LDL by platelets and (iii) the role of activated platelets and ox-LDL in atherosclerosis. In addition, we elaborate on the clinical implications of these interactions, including development of the new therapeutic possibilities. The ability to understand and modulate mechanisms governing interactions between LDL-cholesterol and platelets may offer new treatment strategies for atherosclerosis prevention.
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