Cardiovascular Protective Effects Research Articles

Unique cardiometabolic factors in women that contribute to modified cardiovascular disease risk.

Major risk factors of cardiovascular disease (CVD) include hypertension, obesity, diabetes mellitus and metabolic syndrome; all of which are considered inflammatory conditions. Women are disproportionately affected by inflammatory conditions, with sex differences emerging as early as adolescence. Hormonal fluctuations associated with reproductive events such as menarche, pregnancy and menopause, are hypothesized to promote a pro-inflammatory state in women. Moreover, women who have experienced inflammatory-type conditions such as polycystic ovarian syndrome (PCOS), gestational diabetes or pre-eclampsia, have a cardiometabolic phenotype that pre-disposes to increased risk of myocardial infarction, stroke and coronary heart disease. Women with no notable CVD risk factors are often relatively protected from CVD pre-menopause; but overtake men in risk of major cardiovascular events when the cardiovascular protective effects of oestrogen begin to wane. Sex differences and female-specific factors have long been considered challenging to study and this has led to an underrepresentation of females in clinical trials and lack of female-specific data from pre-clinical studies. However, there is now a clear prerogative to include females at all stages of research, despite inherent complexities and potential variability in data. This review explores recent advancements in our understanding of CVD in women. We summarise the underlying factors unique to women that can promote CVD risk factors, ultimately contributing to CVD burden and the emerging therapies aimed to combat this.

Effects of sodium-glucose co-transporter inhibitors on individual clinical endpoints and quality of life.

Sodium-glucose co-transporter inhibitors (SGLTis) have cardiovascular protective effects. We aimed to assess the effects of SGLTis on individual hard clinical endpoints and quality of life (QoL) in patients with cardiovascular risk factors. Data was searched in PubMed, Embase, Cochrane Library and clinicaltrials.gov databases up to February 2024. Randomized controlled trials (RCTs) comparing SGLTis with placebo were included. The primary outcomes were individual hard clinical endpoints (Subset A) and QoL (Subset B). For Subset A, 13 RCTs including 90413 patients were enrolled (age 66±10.1years, 35.7% female, follow-up 2.4±0.3years); as compared with placebo, SGLTis were associated with significantly lower risk of all-cause mortality [risk ratio (RR): 0.90, 95% confidence interval (CI): 0.86-0.94, P<0.01], cardiovascular mortality (RR: 0.87, 95% CI: 0.82-0.92, P<0.01), hospitalization for heart failure (HF) (RR: 0.72, 95% CI: 0.68-0.76, P<0.01), HF events (RR: 0.72, 95% CI: 0.68-0.75, P<0.01), hospitalization for any cause (RR: 0.91, 95% CI: 0.88-0.93, P<0.01) and myocardial infarction (MI) (RR: 0.92, 95% CI: 0.85-0.99, P=0.03). Notably, the favourable effect of SGLTis on all-cause mortality was more pronounced in younger (<65years) patients (RR: 0.86, 95% CI: 0.81-0.92) and in studies with less female (RR: 0.84, 95% CI: 0.79-0.90). The favourable effect of SGLTis on MI was only observed in patients who received sotagliflozin (RR: 0.47, 95% CI: 0.31-0.73). For Subset B, nine RCTs including 2552 HF patients were enrolled (age 67.8±12.4years, 36.4% female, follow-up 3.4±1.9months); SGLTis were associated with significant improvement in QoL as compared with placebo. In patients with a broad spectrum of cardiovascular risk factors, SGLTis substantially improve individual hard clinical outcomes and QoL.

Dapagliflozin alleviates high-fat-induced obesity cardiomyopathy by inhibiting ferroptosis.

Dapagliflozin (Dapa) is a novel hypoglycaemic agent with multiple cardiovascular protective effects, and it is widely used in treatment of heart failure patients, but whether it can improve obese phenotype of heart failure and its mechanism is still unclear. Ferroptosis is an iron dependent form of cell death and has been proved to be an important role in heart failure. The aim of this study is to determine whether Dapa improves obesity-related heart failure by regulating ferroptosis in high-fat diet rats. Male SD rats were fed a high-fat diet for 12 weeks and confirmed of obese heart failure by metabolic parameters and cardiac ultrasound. Being overweight by 20% compared with the normal group, with elevated systolic blood pressure and abnormal levels of insulin and blood lipid (TG and LDL-c), is recognized as obesity. The obese rats with reduced EF, FS, and E/A shown on ultrasound are defined as the obese heart failure (OHF) group. Histological tests confirmed the more pronounced cardiac fibrosis, mitochondrial volume and collagen deposition in OHF group. Dapa treatment effectively reduced body weight, INS, ISI/IRI index, TG and HDL-C levels (P < 0.05). Also, Dapa administration can slightly decrease the SBP and DBP levels; however, there was no statistical difference among those four groups. Furthermore, Dapa treatment can significantly improve high-fat induced systolic and diastolic dysfunction via regulating cardiac histological abnormalities, including less obvious mitochondrial swelling, muscle fibre dissolution and collagen deposition. Additionally, genes from the OHF group were used by GO enrichment analysis, and it shows that ferroptosis metabolic pathway participated in the development of obese phenotype of heart failure. More importantly, Dapa significantly inhibited Fe2+ and MDA levels (P < 0.05), but augmented GSH content (P < 0.05). In addition, the mRNAs and protein expression of some important regulators of ferroptosis, like GPX4, SLC7A11, FTH1 and FPN1, were all decreased after Dapa intervention. Dapa improved high-fat induced obese cardiac dysfunction via regulating ferroptosis pathway.

Perilla Seed Oil and Protein: Composition, Health Benefits, and Potential Applications in Functional Foods.

Perilla (Perilla frutescens) seeds are emerging as a valuable resource for functional foods and medicines owing to their rich oil and protein content with diverse nutritional and health benefits. Perilla seed oil (PSO) possesses a high level of a-linolenic acid (ALA), a favorable ratio of unsaturated to saturated fatty acids, and other active ingredients such as tocopherols and phytosterols, which contribute to its antioxidant, anti-inflammatory, and cardiovascular protective effects. The balanced amino acid ratio and good functional properties of perilla seed protein make it suitable for a variety of food applications. The chemical composition, health benefits, and potential applications of PSO as well as the structural characterization, functional properties, modification methods, bioactivities, and application scenarios of perilla seed protein are comprehensively presented in this paper. Furthermore, the challenges as well as future prospects and research focus of PSO and perilla seed protein are discussed. The growing interest in plant-based diets and functional foods has made PSO and perilla seed protein promising ingredients for the development of novel foods and health products. The purpose of this paper is to highlight implications for future research and development utilizing these two untapped resources to improve human health and nutrition.

The Role of Exercise in Regulating the Generation of Extracellular Vesicles in Cardiovascular Diseases.

Extracellular vesicles (EVs) are nanoscale vesicles released by cells, which play an important role in intercellular communication by transporting proteins, lipids, nucleic acids, and other molecules. Different intensities of exercise can induce the release of EVs from cells and tissues, such as endothelial cells, skeletal muscle and adipose tissue, hepatocytes, immune cells, and neuronal cells. Exercise-induced EVs exert cardiovascular protective effects such as anti-inflammatory and anti-oxidative by altering their contents. This paper reviews the cell and tissue sources of EVs induced by exercise of different intensities, the regulatory effects of different exercise intensities on EVs, and their mechanisms of action in cardiovascular diseases. The aim is to provide new insights for the treatment of cardiovascular diseases and offer scientific evidence for the construction of engineered EVs mimicking the effects of exercise.

Canagliflozin Mediates Mitophagy Through the AMPK/PINK1/Parkin Pathway to Alleviate ISO-induced Cardiac Remodeling.

Heart failure has always been a prevalent, disabling, and potentially life-threatening disease. For the treatment of heart failure, controlling cardiac remodeling is very important. In recent years, clinical trials have shown that sodium-glucose cotransporter-2 (SGLT-2) inhibitors not only excel in lowering glucose levels but also demonstrate favorable cardiovascular protective effects. However, the precise mechanisms behind the cardiovascular benefits of SGLT-2 inhibitors remain elusive. In this research, we assessed the impact of canagliflozin (CANA, an SGLT-2 inhibitor) on cardiac remodeling progression in mice and preliminarily elucidated the possible mechanism of action of the SGLT-2 inhibitor. Our results indicate that the administration of canagliflozin significantly attenuates myocardial hypertrophy and fibrosis and enhances cardiac ejection function in mice with isoprenaline (ISO)-induced cardiac remodeling. Notably, excessive mitophagy, along with mitochondrial structural abnormalities observed in ISO-induced cardiac remodeling, was mitigated by canagliflozin treatment, thereby attenuating cardiac remodeling progression. Furthermore, the differential expression of AMPK/PINK1/Parkin pathway-related proteins in ISO-induced cardiac remodeling was effectively reversed by canagliflozin, suggesting the therapeutic potential of targeting this pathway with the drug. Thus, our study indicates that canagliflozin holds promise in mitigating cardiac injury, enhancing cardiac function, and potentially exerting cardioprotective effects by modulating mitochondrial function and mitophagy through the AMPK/PINK1/Parkin pathway.

The role of maintaining lower LDL-C level during statin treatment for advanced CKD patients

Background and aimsDifferent from other high cardiovascular (CV) risks populations, the evidence supporting the CV protective effect of LDL-C reduction with statins in chronic kidney disease (CKD) patients is comparatively scarce. This study is aimed to investigate the role of maintaining lower LDL-C level in advanced CKD patients. MethodsBy using Chang Gung Research Database, on the basis of Taiwan's largest healthcare group, a total of 5367 adult patients newly-diagnosed with stage 4 CKD and receiving statin were extracted and further categorized into three groups based on their LDL-C levels: <70 mg/dL, 70–100 mg/dL, and ≥100 mg/dL. The main outcome is major adverse cardiac and cerebrovascular events (MACCEs), a composite of cardiovascular death, myocardial infarction, and stroke. The inverse probability of treatment weighting was performed to achieve balance of baseline characteristics. ResultsAt 5-year follow-up, the LDL-C < 70 mg/dL group exhibited significantly lower risks of MACCEs (14.3 % vs. 18.7 %, hazard ratio [HR]: 0.77, 95 % CI: 0.69–0.86), cardiovascular death (7.1 % vs. 9.7 %, subdistribution HR [SHR]: 0.75, 95 % CI: 0.65–0.88), ischemic stroke (4.1 % vs. 5.4 %, [SHR]: 0.65, 95 % CI: 0.54–0.79), and new-onset end-stage renal disease requiring chronic dialysis (25.6 % vs. 29.4 %, SHR: 0.87, 95 % CI: 0.80–0.91) compared to LDL-C > 100 mg/dL group. In contrast, the group with LDL-C levels between 70 and 100 did not significantly differ from the group with LDL-C > 100 mg/dL in study outcomes. ConclusionsMaintaining LDL-C lower than 70 mg/dL may be beneficial for cardiovascular protection in advanced CKD patients and a lower LDL-C treatment target may be required as CKD progression.

SGLT2 inhibitor, a new bullet in heart failure management

The global health landscape is confronted with substantial challenges stemming from diabetes mellitus and heart failure (HF). The escalating incidence of diabetes mellitus (DM), in correlation with HF, underscores the imperative necessity for efficacious strategies in the realm of prevention and management. The most recent advancements in therapeutic approaches, specifically Sodium-glucose transporter 2 inhibitors (SGLT2i), present a promising prospect for enhancing outcomes and addressing the existing gaps in HF management. This paper aims to elucidate the significance of SGLT2i in the therapeutic management of both reduced and preserved heart failure, with or without the presence of DM. SGLT2i are new heart failure drugs. In trials, SGLT2i improved diastolic dysfunction, reduced oxidative stress, inflammation, fibrosis, and myofilament rigidity. The first SGLT2 inhibitor studies, EMPA-REG OUTCOME, DECLARE-TIMI 58, and CANVAS, showed that Empagliflozin and Canagliflozin reduced HF mortality and rehospitalization in type 2 diabetes mellitus (T2DM) patients. Dapagliflozin reduces HF hospitalizations without impacting T2DM mortality. Canagliflozin avoided creatinine rises, kidney disease deaths, and cardiovascular deaths in the CREDENCE Study. SGLT2i improve health in heart failure with preserved ejection fraction (HFpEF). SGLT2i improved health status statistically in the PRESERVED-HF and EMPEROR-Preserved investigations. SGLT2i became known as a promising therapeutic choice in the treatment of HF. The substantial evidence from prominent large-scale clinical trials has substantiated the cardiovascular and renal protective effects of SGLT2i. Furthermore, the benefits of these medications are relevant for individuals who have been diagnosed with heart failure with reduced ejection fraction (HFrEF), as well as those who are experiencing heart failure with preserved ejection fraction (HFpEF). Keyword: diabetes mellitus, heart failure, management, SGLT2 inhibitor

Sex differences in outcomes of percutaneous left atrial appendage closure

Abstract Background Atrial fibrillation (AF) is the most common arrhythmia in adults and is associated with an increased risk of embolic stroke. In a previous survey, 91% of nonrheumatic AF-related left atrial thrombi was originated in the left atrial appendage (LAA). Percutaneous left atrial appendage closure (LAAC) with the Watchman device has been shown to be noninferior to anticoagulation therapy in clinical trials for stroke prevention in nonrheumatic AF. It has been used in Japan since September 2019 only for patients who are at the high risk of bleeding events. The WATCHMAN family is the only left atrial appendage closure (LAAC) device in Japan. Since long time ago, sex differences have been attracting attention in the cardiology. Due to the cardiovascular protective effects of endogenous estrogens, premenopausal women are thought to be less likely to develop cardiovascular disease. Whereas, in area of AF, Female with AF have higher stroke risk and female with AF have severe after effect. However, there are few studies on sex differences in LAAC implantation outcomes. Purpose We aimed to identify the sex differences of outcomes of LAAC in Japanese patients. Methods A total of 118 consecutive patients who underwent LAAC at our hospital from January 2020 to August 2023 were prospectively analyzed. Various patient characteristics, comorbidities, and outcomes were identified and compared between male and female. Results Results are shown in Table. Female were older (79 vs. 73 years, p = 0.0009), thinner (Body mass index 22 vs. 24 kg/m2, p = 0.0326), and less likely to have had diabetes (19 vs. 40%, p = 0.0340). Pulmonary embolism was significantly more common in female after LAAC. If anticoagulants are discontinued after LAAC, women’s susceptibility to coagulation may become apparent. Conclusions LAAC was feasible and safe for Japanese patients of both genders. However, these results could have a relevant impact on the antithrombotic management of patients who are at the high risk of embolic considering sex difference. Especially, we should pay great attention when discontinuing anticoagulants after LAAC in female.

Restoration of autophagy reduces diabetes-induced endothelial dysfunction

Abstract Introduction Diabetes leads to endothelial dysfunction, a main determinant of several cardiovascular diseases. The molecular mechanisms underlying the effects of hyperglycemia in endothelial cells are not fully characterized. Autophagy, the intracellular process by which the cell digests and recycles senescent or damaged cytoplasmic elements, exerts cardiovascular protective effects, limiting cardiac and vascular injury in the presence of stress. However, it is unclear how hyperglycemia modulates autophagy in endothelial cells. Purpose In this study, we elucidated the role of autophagy in vascular damage induced by diabetes. We also tested whether the restoration autophagy attenuates diabetes-induced endothelial damage. Methods We evaluated the effects of high-glucose (HG, 30 mM for 6 and 24 hours) on markers of endothelial function, autophagy, autophagic flux, and mitophagy in human umbilical endothelial cells (HUVEC) in vitro and in mesenteric arteries from wild-type mice (WT) ex vivo. We tested the effects of autophagy reactivation using the natural polyamine spermidine or ATG7 overexpression (ATG7ov) on apoptosis and angiogenesis in HUVEC treated with HG. Vascular reactivity experiments in the presence of autophagy activation were performed in HG-treated mouse mesenteric arteries and human saphenous veins from patients with peripheral artery disease. Finally, we evaluated the level of autophagy in the mammary arteries of newly discovered diabetic patients undergoing coronary artery bypass graft surgery. Results We found that HG reduces autophagy (0.6 fold p&amp;lt;0.05) and mitophagy (1.5 fold p&amp;lt;0.001) in HUVECs. We also demonstrated that endothelial cells undergoing hyperglycemia fail to activate autophagy under hypoxic conditions (0.6 fold p&amp;lt;0.05). Reactivation of autophagy by ATG7ov rescues apoptosis (0.52 fold p&amp;lt;0.05) and angiogenesis (2.3 fold p&amp;lt;0.05) in HUVEC treated with HG. We further observed that HG exacerbates endothelial dysfunction in a mouse model of genetic inhibition (Beclin 1 +/- mice), compared to WT mice (-19.16 % +-4.97 SEM vs -48.39 % +-2.18 SEM p&amp;lt;0.001). Mechanistically, HG increases cellular acetylation status (0.7 fold p&amp;lt;0.05) and activates p300 (1 fold p&amp;lt;0.05), an autophagy inhibitor. ATG7ov or spermidine, a p300 inhibitor, rescue endothelial-dependent relaxation in mesenteric arteries of WT mice treated with HG (ATG7ov -62.48 % +-5.16 SEM; SP -63.01 +-3.22 SEM; HG -40.67 % +-3.82 p&amp;lt;0.001). Finally, we observed reduced levels of autophagy in mammary arteries from diabetic patients and demonstrated that SP improves vascular function in human saphenous veins (-37.6 % +-12.76 SEM vs -12.52 % +-5.6 SEM p&amp;lt;0.001). Conclusion Our results suggest that the impairment of autophagy is a strong contributor of diabetes induced-endothelial dysfunction. Targeting autophagy may represent a valid therapeutic strategy to counteract the cardiovascular consequences of metabolic stress.

Low levels of apolipoprotein M are associated with increased risk of ventricular arrhythmias

Abstract Background Ventricular arrhythmia (VA) is a frequent cause of sudden cardiac death (SCD). Treatment to prevent SCD includes device therapy with implantable cardioverter defibrillator (ICD). Although the electrophysiology underlying VA have been described, the molecular understanding of VA risk remains unclear. Purpose To identify proteins that are associated with higher and lower risk of VA. Methods SMASH 1 Study was a prospective observational study of 490 patients treated with ICD. The plasma proteome was analyzed with the Olink Explore 384 Cardiometabolic platform at study inclusion, and patients were followed for mean 3.1± 0.7 years. VA events were defined as adjudicated ventricular fibrillation or sustained ventricular tachycardia registered from ICD recordings and clinical events were recorded from electronic health records. Protein concentrations were quantified relatively as normalized protein expression on a log2-transformed concentrations where a large number represents higher protein level in the sample. Results The mean age was 66±12 years, 83% were male and 51% had a primary prevention ICD-indication. Episode(s) of VA occurred in 137 patients (28%) during follow-up. In total, 353 distinct proteins were successfully analyzed in all patients. Among these, high B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) levels were associated with a higher risk of VA, while Apolipoprotein M (APOM) was the only protein significantly associated with a lower risk of VA after multiple testing using Benjamini-Hochberg correction (Figure, Panel A). After adjusting for age, sex, body mass index, coronary artery disease, heart failure, renal function, left ventricular ejection fraction and antiarrhythmic medication, only low APOM levels remained significantly associated with VA: HR 0.51 (95%CI 0.32-0.79] per log unit increase, p=0.003. Patients in the lowest quartile of APOM had a particularly high risk of incident VA: HR 2.26 (95%CI 1.60-3.19), p=3.61x10-6, compared to quartile 2-4 (Figure, Panel B). High APOM levels were also associated with a lower risk of HF hospitalizations (HR 0.25 [95%CI 0.16-0.40], p&amp;lt;0.001) and all-cause mortality (HR 0.36 [95%CI 0.22-0.60], p&amp;lt;0.001), and these associations remained significant in adjusted models. Conclusions Low levels of APOM are associated with a greater risk of incident VA, independently of established risk factors. Low APOM also predicted risk of HF hospitalizations and mortality in our cohort, which suggest protective cardiovascular effects of APOM. Figure: Association of individual proteomic measures with risk of ventricular arrhythmias (VA).A:Volcano plots of the associations of individual plasma proteins with incident VA. The dotted line represents the significance level at false discovery rate &amp;lt;0.05 and the red dots are significant proteins after multiple testing using Benjamini-Hochberg correction.B: Risk of VA by quartile of Apolipoprotein M.

Comprehensive Evaluation of the Cardiovascular Protective Effects of Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Advanced Chronic Kidney Disease: A Real-World Evidence

Introduction: Diabetes, kidney disease, and cardiovascular disease have complex interactions and coexistences that significantly worsen a patient’s overall health. Previous research results have shown that SGLT2i hypoglycemic drugs can not only effectively control blood sugar in diabetic patients but also protect the kidneys and heart. This study further focuses on diabetic patients with kidney disease to explore the effectiveness of using SGLT2i hypoglycemic drugs in avoiding heart-related complications or death. Methods: This is a multicenter retrospective cohort study using the Taipei Medical University Clinical Research Database (TMUCRD) as the data source. This study selected patients who suffered from both type 2 diabetes and chronic kidney disease from 1 January 2008 to 31 December 2020, as the research team. Integrated or separate 4-point major adverse cardiovascular events (4P-MACE) and mortality were the outcomes of this study. The Kaplan-Meier curves method and Cox proportional hazard regression analysis were used to explore the association between each influencing factor and the outcome. Results: A total of 5,005 patients with type 2 diabetes and CKD were included in this study, of which 524 patients were stably treated with SGLT2i, 3,952 patients were treated with DPP4i, and 529 patients were treated with TZD. The results showed that the SGLT2i user group had a significantly lower risk of 4P-MACE compared with the SGLT2i nonuser group (hazard ratio [HR]: 0.68, 95% CI [0.49, 0.95], p = 0.024). The SGLT2i group had a significantly lower risk of cardiovascular mortality compared with the DPP4i and TZD groups (HR: 0.37, 95% CI [0.21, 0.65], p < 0.001; HR: 0.42, 95% CI [0.20, 0.90], p = 0.025). Conclusion: This study found that for patients with both diabetes and kidney disease, SGLT2i is a better option than other oral hypoglycemic medications because it can significantly avoid the occurrence of heart-related complications. The results of this study can be used as a reference for clinical medication selection practice.

Exploring the Cardiovascular Protective Effects of Baicalin: A Pathway to New Therapeutic Insights.

Cardiovascular disorders develop the highest rates of mortality and morbidity worldwide, emphasizing the need for novel pharmacotherapies. The Chinese medicinal plant S. baicalensis has a number of major active components, one of which is called baicalin. According to emerging research, baicalin reduces chronic inflammation, immunological imbalance, lipid metabolism, apoptosis, and oxidative stress. Baicalin improves endothelial function and protects the cardiovascular system from oxidative stress-induced cell injury by scavenging free radicals and inhibiting xanthine oxidase. Therefore, it helps prevent CVD such as hypertension, atherosclerosis, and cardiac arrest. In this review, the therapeutic effects of baicalein are discussed in relation to both the prevention and management of cardiovascular diseases.

Dihydrotanshinone I promotes LDL uptake by HepG2 cells through increasing LDLR level

ABSTRACT Dihydrotanshinone I (DHT), a lipophilic compound extracted from Salvia miltiorrhiza, has cardiovascular protective effects, but the underlying molecular mechanisms of action have rarely been reported. Based on this, whether DHT affects cholesterol metabolism by regulating LDLR is investigated in this work. The results revealed that DHT can increase LDLR expression and promote LDL uptake by HepG2 cells. Meanwhile, DHT stabilizes LDLR mRNA expression by activating the epidermal growth factor receptor/extracellular signal-regulated kinase 1/2 (EGFR/erk1/2) signaling pathway. In addition, DHT inhibits the expression of the proprotein convertase subtilisin/kexin type 9 (PCSK9) by down-regulating the liver nuclear transcription factor 1 A (HNF1A) and up-regulating the forkhead box O3 (FOXO3). All of these indicate that DHT increases LDLR expression at the post-transcriptional and post-translational levels thereby promoting LDL-C metabolism. The potential mechanism of DHT to improve lipid metabolism has been revealed as a promising drug against AS.

The Role of Social Determinants in Alcohol Consumption and Cardiovascular Health: The Pathways Study

Background and AimsThe "J"-shaped relationship between alcohol consumption and cardiovascular health is recognized as potentially influenced by residual confounders, and this study aimed to clarify the role that social determinants play in the relationship. Methods and ResultsUsing NHANES data from 2005-2018, this study analyzed 30,648 participants to assess how eight social determinants (employment, income, food security, education, healthcare access, insurance, housing stability, and marital status) influence the relationship between alcohol consumption and cardiovascular disease (CVD). Moderate drinking reduces CVD risk (HR: 0.741, 95%CI: 0.661, 0.831, P<0.001), while heavy drinking increases it (HR: 1.025, 95%CI: 1.004, 1.095, P=0.035). Structural equation modeling revealed that ideal social determinants and health metrics contribute significantly to the cardiovascular protective effects of moderate drinking (path proportion: 42.31%). Conversely, heavy drinking is associated with poorer social determinants and health metrics, masking the cardiovascular protective effect (path proportion: -90.91%). ConclusionsThis study quantifies the role of social and health factors in the relationship between alcohol consumption and CVD. Despite identifying direct cardiovascular protective effects of alcohol consumption, global health initiatives should continue to advocate for reduced heavy drinking, given the significant risks involved.

Current vaccination and immunization strategies in dermatology

Vaccinations are an important pillar of public health. They have high benefits for individuals and society as awhole by specifically preventing or mitigating infectious diseases. In many cases, they offer benefits that go beyond protection against the disease in question, e.g., protective cardiovascular effects. Vaccination recommendations in Germany are drawn up by the Standing Committee on Vaccination (STIKO), while the European Medicines Agency (EMA) is responsible for the approval of vaccines in the EU. Vaccinations may be carried out by physicians regardless of their specialty. In dermatology, vaccinations against varicella (chickenpox), herpes zoster, and human papillomavirus are established. The development of vaccines against other dermatologically relevant diseases and cancer vaccines is the subject of intensive research. Particularly in the case of immunosuppression, the physician must also take into consideration which vaccinations are possible and useful or contraindicated. TypeI or typeIV allergies to components of vaccinations are very rare, but reactions at the injection site often occur as adermatological side effect. Urticarial reactions are also possible, as does the worsening of underlying dermatological conditions such as psoriasis vulgaris.

Review on the pharmacological effects and pharmacokinetics of scutellarein.

Scutellarein is a flavonoid from Scutellaria baicalensisGeorgi that has been shown to have a variety of pharmacological activities. This review aims to summarize the pharmacological and pharmacokinetic studies on scutellarein and provide useful information for relevant scholars. Pharmacological studies indicate that scutellarein possesses a diverse range of pharmacological properties, including but not limited to anti-inflammatory, antioxidant, antiviral, neuroprotective, hypoglycemic, hypolipidemic, anticancer, and cardiovascular protective effects. Further investigation reveals that the pharmacological effects of scutellarein are driven by multiple mechanisms. These mechanisms encompass the scavenging of free radicals, inhibition of the activation of inflammatory signaling pathways and expression of inflammatory mediators, inhibition of the activity of crucial viral proteins, suppression of gluconeogenesis, amelioration of insulin resistance, improvement of cerebral ischemia-reperfusion injury, induction of apoptosis in cancer cells, and prevention of myocardial hypertrophy, among others. In summary, these pharmacological studies suggest that scutellarein holds promise for the treatment of various diseases. It is imperative to conduct clinical studies to further elucidate the therapeutic effects of scutellarein. However, it is worth noting that studies on the pharmacokinetics reveal an inhibitory effect of scutellarein on uridine 5'-diphosphate glucuronide transferases and cytochrome P450 enzymes, potentially posing safety risks.

The Role of miRNA-29b1 on the Hypoxia-Induced Apoptosis in Mammalian Cardiomyocytes

A hypoxic stress which causes apoptosis of cardiomyocytes is the main problem in the ischemic heart disease. The present research sought to investigate the role of microRNA-29b1 (miR-29b1) in hypoxia-treated cardiomyocytes and its potential mechanism involved. We replicated an in vitro AC16 and H9C2 cardiomyocytes ischemia model by hypoxia (1% O2, 48 h) treatment. Cell apoptosis was evaluated by flow cytometry using Annexin V FITC-PI staining assay. Moreover, we used western blot and immunofluorescence analysis to determine the expression of Bcl-2, Bax caspase-3 and Cx43 proteins. We found that miR-29b1 protected AC16 and H9C2 cells from hypoxia-induced injury as the evidences that miR-29b1 attenuated the effects of hypoxia treatment on AC16 and H9C2 cell apoptosis after hypoxia treatment. In conclusion, these results revealed the potential cardiovascular protective effects of miR-29b1 in the process of ischemia-related myocardial injury.

Cardioprotective Effects of Exercise: The Role of Irisin and Exosome.

Exercise is an effective measure for preventing and treating cardiovascular diseases, although the exact molecular mechanism remains unknown. Previous studies have shown that both irisin and exosomes can improve the course of cardiovascular disease independently. Therefore, it is speculated that the cardiovascular protective effect of exercise is also related to its ability to regulate the concentrations of irisin and exosomes in the circulatory system. In this review, the potential synergistic interactions between irisin and exosomes are examined, as well as the underlying mechanisms including the AMPK/PI3K/AKT pathway, the TGFβ1/Smad2/3 pathway, the PI3K/AKT/VEGF pathway, and the PTEN/PINK1/Parkin pathway are examined. This paper provides evidence to propose that exercise promotes the release of exosomes enriched with irisin, miR-486-5p and miR-342-5p from skeletal muscles, which results in the activation protective networks in the cardiovascular system. Moreover, the potential synergistic effect in exosomal cargo can provide new ideas for clinical research of exercise mimics.

Abstract P447: Impact of Altered Receptor Expression On the Cardiovascular Response to Estrogen

Premenopausal women benefit from estrogen's protective effects, including lower arterial stiffness than men of the same age. Despite estrogen's protective role, menopausal hormone therapy showed no cardiovascular benefits in the Women's Health Initiative. One theory is that the response to menopausal hormone therapy is modulated by the presence of pre-existing cardiovascular disease. Estrogen signals through nuclear estrogen receptors ERα and ERβ, and the membrane-bound G protein-coupled estrogen receptor (GPER). Our lab has shown that GPER induces protective cardiovascular effects including decreased blood pressure, protection from renal damage, and attenuation of arterial remodeling. In this study, we hypothesized that GPER deletion would attenuate the protective vascular effects of estrogen after menopause. Female C57Bl/6J wildtype (wt) and global GPER knockout (ko) mice underwent ovariectomy (OVX) at 46 weeks of age and concurrently administered estrogen (E) or vehicle (Veh). Angiotensin II (Ang II; 700 ng/kg/day) infusion was used to induce hypertension either four weeks prior (Ang-E) or at the time of OVX (E-Ang) to evaluate the impact of cardiovascular diseases preceding or coinciding with menopause. Blood pressure was measured by tail-cuff plethysmography and arterial stiffness was assessed by pulse wave velocity (PWV). Statistical analysis was performed using one-way ANOVA. Ang II induced a similar level of hypertension in wt and ko mice and was not impacted by E or timing. In wt mice, PWV was significantly higher in Veh-treated compared with E-treated hypertensive animals, independent of timing (P&lt;0.001). In contrast, PWV was not impacted by E in GPER ko mice (P=0.99). In conclusion, we found that E did not affect the hypertensive response to Ang II in both wt and GPER ko mice. GPER deletion reduced estrogen’s protection from arterial stiffening. Whether Ang II preceded or coincided with menopause did not alter the effects of E. These studies are important for determining whether cardiovascular status should be a factor when considering menopausal hormone therapy.