Related Cardiovascular Diseases Research Articles

Lipoprotein lipase as a target for obesity/diabetes related cardiovascular disease

Worldwide, the prevalence of obesity and diabetes have increased, with heart disease being their leading cause of death. Traditionally, the management of obesity and diabetes has focused mainly on weight reduction and controlling high blood glucose. Unfortunately, despite these efforts, poor medication management predisposes these patients to heart failure. One instigator for the development of heart failure is how cardiac tissue utilizes different sources of fuel for energy. In this regard, the heart switches from using various substrates, to predominantly using fatty acids (FA). This transformation to using FA as an exclusive source of energy is helpful in the initial stages of the disease. However, over the progression of diabetes this has grave end results. This is because toxic by-products are produced by overuse of FA, which weaken heart function (heart disease). Lipoprotein lipase (LPL) is responsible for regulating FA delivery to the heart, and its function during diabetes has not been completely revealed. In this review, the mechanisms by which LPL regulates fuel utilization by the heart in control conditions and following diabetes will be discussed in an attempt to identify new targets for therapeutic intervention. Currently, as treatment options to directly target diabetic heart disease are scarce, research on LPL may assist in drug development that exclusively targets fuel utilization by the heart and lipid accumulation in macrophages to help delay, prevent, or treat cardiac failure, and provide long-term management of this condition during diabetes.

Orexin 1 Receptors in The Paraventricular Nucleus of The Hypothalamus (PVN) Facilitate The Peripheral Chemoreflex

Increased sensitivity of the peripheral chemoreflex (PCR) to hypoxia is associated with cardiovascular-related diseases such as hypertension and heart failure. We previously showed that systemic blockade of both orexin 1 (Ox1R) and orexin 2 receptors reduced the PCR-mediated hypoxic ventilatory response (HVR), and that hypoxia activates PVN-projecting orexin neurons. The effect of OxR blockade on the HVR was strongest in the active phase of the circadian cycle and was associated with decreased numbers of activated neurons in the nucleus of the solitary tract (nTS) and nTS-projecting corticotropin-releasing neurons in the PVN. While the projection from the PVN to the nTS contributes to the PCR, the neuronal mechanism(s) activating this projection are unclear. We hypothesized that orexin acting at Ox1R in the PVN facilitates the PCR. To test this hypothesis, we first performed IHC to confirm the expression of Ox1R in the PVN. We then assessed the degree to which specific Ox1R blockade reduced the HVR (n=6; tested first with vehicle (100% DMSO), then Ox1R antagonist SB-334867, 1 mg/kg, i.p). To assess the contribution of PVN Ox1Rs to the PCR as well as the associated activation of neurons in the PVN and nTS, we specifically knocked down Ox1R expression in the PVN via nanoinjection of an Ox1R shRNA-GFP expressing AAV vector. Rats were exposed to graded hypoxia during the active phase, with inspired O2 taken from 21% to 11% over a ~5 min period. Rats were kept near-isocapnic by slightly increasing the inspired CO2. Subsets of rats were exposed to hypoxia to assess the effects of Ox1R on neuronal activation using c-Fos expression as a surrogate marker. Systemic Ox1R blockade significantly reduced the HVR compared to the control response (by ~30%; p=0.0027). Knockdown of Ox1R in the PVN also reduced the HVR (by ~20%; p=0.049) and reduced the number of c-Fos expressing PVN neurons in response to hypoxia (p=0.0232). More specifically, hypoxia induced c-Fos expression in fewer PVN neurons transfected with Ox1R shRNA (confirmed by GFP expression) than neurons from control rats transfected with scrambled RNA (p=0.0083). Ox1R knockdown in the PVN also significantly reduced the hypoxia-induced increase in number of c-Fos expressing tyrosine-hydroxylase (TH) nTS neurons (p=0.0303), suggesting that PVN Ox1Rs mediate hypoxia-induced activation of TH neurons in the nTS. These findings suggest that in the PVN, orexin acting at Ox1Rs mediate the facilitation of the PCR and the associated activation of the PVN and nTS neurons. Ox1R in the PVN could be a novel target to treat diseases associated with increased PCR sensitivity. Grants: 5R01HL098602 (to DK, EH and KC). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effect of Sodium Fluoride on Oxidative Stress and Antioxidant System in Male Wistar Rats

This research aimed to examine the effect of sodium fluoride (NaF) on oxidative stress and antioxidant systems in the serum, aorta, and cardiac tissues of male Wistar rats. The increased attention to sodium fluoride and its detrimental effects on human health in recent years has led to concerns. Excessive ingestion and accumulation of sodium fluoride from water, toothpaste, and pesticides could initiate oxidative stress in the blood, aorta, and heart. This heightened oxidative stress and disturbance in the antioxidant system pose a significant risk and may predispose the body to severe vascular and cardiovascular-related diseases, which are leading causes of global mortality. In this study, ten male Wistar rats weighing 150-180g were grouped into two (n=5). Group I Control received distilled water, and Group 2 received 10mg/kg NaF orally for 21 days. Markers of oxidative stress malondialdehyde (MDA) and reduced glutathione (GSH), antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and total antioxidant capacity (TAC) were measured in the serum, aorta, and heart. Data were analyzed using descriptive statistics of student t-test at α0.05. The data were presented as mean ± SEM. The oral administration of sodium fluoride resulted in an elevation of MDA levels in the serum, aorta, and heart of the rats exposed to NaF. Additionally, the oral administration of sodium fluoride led to a reduction in superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) levels in the serum, aorta, and heart of rats exposed to NaF. Furthermore, the oral administration of sodium fluoride resulted in a decrease in the total antioxidant capacity (TAC) in the serum, aorta, and heart of rats exposed to sodium fluoride. This study demonstrated that sodium fluoride exposure diminishes the antioxidant capacity in the serum, aorta, and heart, indicating that sodium fluoride exposure induces oxidative stress, potentially affecting the functions of the aorta and heart. Therefore, the continuous exposure to fluoride in populations residing in regions with endemic fluorosis worldwide should be a topic of considerable concern. This research work was self-funded. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Role of ASIC3 in Evoking the Exercise Pressor Reflex in Type 1 Diabetes Mellitus Rats

Previous studies have suggested that the exercise pressor reflex is exaggerated in individuals with type 1 diabetes mellitus (T1DM); however, the mechanisms responsible for this altered reflex are poorly understood. Acid-sensing ion channel 3 (ASIC3) likely contributes to this exaggeration as previous studies found that peripheral blockade, as well as functional knockout (KO) of the ASIC3 gene, prevented the exaggeration of exercise pressor reflex in rats with cardiovascular-related diseases. However, whether ASIC3 plays a similar role in the exaggerated exercise pressor reflex in T1DM is currently unknown. Therefore, the purpose of this study was to determine whether ASIC3 contributes to the exaggerated exercise pressor reflex in T1DM rats. We hypothesized that the exaggerated exercise pressor reflex would be attenuated in ASIC3 KO T1DM rats compared to their wild-type (WT) counterparts. To test this, we used adult, male and female Wistar-Kyoto ASIC3 KO (n=3; body weight: 348 ± 84 g) and WT counterparts (n=5; body weight: 318 ± 112 g) rats. Streptozotocin (50 mg/kg) was injected intraperitoneally in fasted anesthetized rats to induce T1DM, and a random blood glucose over 300 mg/dl was used to diagnose diabetes. One week later, the exercise pressor reflex was evoked in unanesthetized, decerebrated rats by statically contracting the hindlimb muscles for 30 s. Peak mean arterial pressure (MAP) and heart rate (HR) were calculated as the highest change (Δ) during 30 s contraction baseline. We found that the peak pressor and cardioaccelerator responses to static contraction, although is not statistically significant, appear to be lower in ASIC3 KO (ΔMAP: 17 ± 14 mmHg; ΔHR: 13 ± 12 bpm), compared to WT rats (ΔMAP: 23 ± 11 mmHg; P=0.26 ΔHR:23 ± 9 bpm; P=0.11). Furthermore, we found that within female rats, the peak pressor and heart rate responses were lower in ASIC3 KO (n=1) rat (ΔMAP: 7 mmHg; ΔHR: 15 bpm) compared to WT rats (n=3) (ΔMAP: 27 ± 12 mmHg; ΔHR: 27 ± 11 bpm). Our preliminary findings suggest that ASIC3 may play a role in the exaggerated exercise pressor reflex in T1DM rats and that sex differences may also be present. Further studies involving larger sample sizes will reveal if trends from the current results become significant. This project was supported by NIH R01HL 166323-01A1. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Cardiovascular mortality risk in patients with ovarian cancer: a population-based study

ObjectivesOvarian cancer (OC) can occur at different ages and is affected by a variety of factors. In order to evaluate the risk of cardiovascular mortality in patients with ovarian cancer, we included influencing factors including age, histological type, surgical method, chemotherapy, whether distant metastasis, race and developed a nomogram to evaluate the ability to predict occurrence. At present, we have not found any correlation studies on cardiovascular death events in patients with ovarian cancer. This study was designed to provide targeted measures for effective prevention of cardiovascular death in patients with ovarian cancer.MethodsKaplan–Meier analysis and multivariable Cox proportional model were performed to evaluate the effectiveness of cardiovascular diseases on overall survival (OS) and ovarian cancer‐specific survival (OCSS). We compared multiple groups including clinical, demographic, therapeutic characteristics and histological types. Cox risk regression analysis, Kaplan–Meier survival curves, and propensity score matching were employed for analyzing the data.ResultsA total of 88,653 ovarian cancer patients were collected, of which 2,282 (2.57%) patients died due to cardiovascular-related diseases. Age, chemotherapy and whether satisfactory cytoreduction surgery is still the most important factors affecting the prognosis of ovarian cancer patients, while different histological types, diagnosis time, and race also have a certain impact on the prognosis. The newly developed nomogram model showed excellent predictive performance, with a C-index of 0.759 (95%CI: 0.757–0.761) for the group. Elderly patients with ovarian cancer are still a high-risk group for cardiovascular death [HR: 21.07 (95%CI: 5.21–85.30), p < 0.001]. The calibration curve showed good agreement from predicted survival probabilities to actual observations.ConclusionThis study found that age, histology, surgery, race, chemotherapy, and tumor metastasis are independent prognostic factors for cardiovascular death in patients with ovarian cancer. The nomogram-based model can accurately predict the OS of ovarian cancer patients. It is expected to inform clinical decision-making and help develop targeted treatment strategies for this population.

Identification of Riluzole derivatives as novel calmodulin inhibitors with neuroprotective activity by a joint synthesis, biosensor, and computational guided strategy

The development of new molecules for the treatment of calmodulin related cardiovascular or neurodegenerative diseases is an interesting goal. In this work, we introduce a novel strategy with four main steps: (1) chemical synthesis of target molecules, (2) Förster Resonance Energy Transfer (FRET) biosensor development and in vitro biological assay of new derivatives, (3) Cheminformatics models development and in vivo activity prediction, and (4) Docking studies. This strategy is illustrated with a case study. Firstly, a series of 4-substituted Riluzole derivatives 1–3 were synthetized through a strategy that involves the construction of the 4-bromoriluzole framework and its further functionalization via palladium catalysis or organolithium chemistry. Next, a FRET biosensor for monitoring Ca2+-dependent CaM-ligands interactions has been developed and used for the in vitro assay of Riluzole derivatives. In particular, the best inhibition (80%) was observed for 4-methoxyphenylriluzole 2b. Besides, we trained and validated a new Networks Invariant, Information Fusion, Perturbation Theory, and Machine Learning (NIFPTML) model for predicting probability profiles of in vivo biological activity parameters in different regions of the brain. Next, we used this model to predict the in vivo activity of the compounds experimentally studied in vitro. Last, docking study conducted on Riluzole and its derivatives has provided valuable insights into their binding conformations with the target protein, involving calmodulin and the SK4 channel. This new combined strategy may be useful to reduce assay costs (animals, materials, time, and human resources) in the drug discovery process of calmodulin inhibitors.

Immunological Implications in Diabetes: A Review on Various Diseases and Conditions

Abstract:: Diabetes Mellitus (DM) is a long-term metabolic condition that has significant social, health, and economic consequences. There are various forms of diabetes mellitus, but the two most common varieties are type I and type II. Insulin-dependent diabetes (IDDM) is one of the most wellknown autoimmune illnesses that cause insulin insufficiency and hyperglycemia by either damaging or destroying Langerhans' beta cells. Available scientific data evidenced the greatest genetic contribution of Human Leukocyte Antigen class II in the IDDM. Hyperglycemia and individual components of the insulin resistance (metabolic) syndrome put people with type II diabetes at increased risk for microvascular consequences (retinopathy, nephropathy, and neuropathy) as well as macrovascular issues (cardiovascular comorbidities). A number of pathophysiological abnormalities, including obesity, poor diet, and physical inactivity, as well as genetic variables, are involved in the disturbed glucose homeostasis associated with type II diabetes. Diseases like lipid abnormalities contribute to the progression of diabetes, whereas obesity and its related medical disorders (such as hypertension, diabetes, insulin resistance, and sleep apnea syndrome) are eventually linked to an elevated cardiovascular risk. Diabetes raises the incidence, intensity, and duration of peri-densities in people with diabetes compared to healthy persons, making it a risk factor for periodontal disease. Diabetes conditions in patients concurrently also increase the progression or risk of other diseases, i.e., cardiovascular- related diseases (hypertension, oxidative stress, hyperlipidemia), nervous system-related diseases, and COVID-19, by increasing the overall infection rate. There is widespread evidence that correlates the direct connection between diabetes and other diseases, including immunity disorders, CVS disorders, etc. This review provides a correlation between diabetes and another disease with an overall impact on the progression of cardiovascular diseases, neurological diseases, COVID-19, and periodontal diseases. This current review focuses on the collation of some plants that show antidiabetic activity, including plant part, family, chemical constituent, mechanism of action, and chemical used for extraction. Studies on the role, causes, clinical management, prevention, and treatment of diabetes heavily rely on epidemiological evidence. This review also explains different factors responsible for diabetes, like genetic factors, environmental factors, and viral infections.

Cardiovascular considerations on recreational scuba diving. SEC-Clinical Cardiology Association/SEC-Working Group on Sports Cardiology consensus document

The practice of recreational scuba diving has increased worldwide, with millions of people taking part each year. The aquatic environment is a hostile setting that requires human physiology to adapt by undergoing a series of changes that stress the body. Therefore, physical fitness and control of cardiovascular risk factors are essential for practicing this sport. Medical assessment is not mandatory before participating in this sport and is only required when recommended by a health questionnaire designed for this purpose. However, due to the significance of cardiovascular disease, cardiology consultations are becoming more frequent. The aim of the present consensus document is to describe the cardiovascular physiological changes that occur during diving, focusing on related cardiovascular diseases, their management, and follow-up recommendations. The assessment and follow-up of individuals who practice diving with previous cardiovascular disease are also discussed. This document, endorsed by the Clinical Cardiology Association of the Spanish Society of Cardiology (SEC) and the SEC Working Group on Sports Cardiology of the Association of Preventive Cardiology, aims to assist both cardiologists in evaluating patients, as well as other specialists responsible for assessing individuals’ fitness for diving practice.

Cilnidipine, a Dual L/N-type Ca2+ Channel Blocker in Hypertension Management: A Review.

Calcium channel blockers (CCBs) are widely used antihypertensive agents due to their effectiveness in reducing blood pressure (BP), along with their good tolerability and evidence of reducing hypertension (HTN)-related cardiovascular and renal diseases. Cilnidipine, a unique dihydropyridine calcium antagonist, exhibits potent inhibitory action on both N-type and L-type voltage-dependent calcium channels. With excellent oral absorption and a prolonged duration of action, it demonstrates a significant antihypertensive effect. It effectively reduces BP both systolic and diastolic while providing renal, neurological, and cardiovascular protection. Unlike L-type CCBs, cilnidipine does not increase pulse rates (PRs) and is associated with reduced occurrence of pedal edema. Cilnidipine is an effective treatment choice for individuals with mild to moderate essential HTN, whether it is administered alone or in conjunction with other treatment modalities.

Has the first year of the COVID pandemic impacted the trends in obesity-related CVD mortality between 1999 and 2019 in the United States?

BackgroundDuring the covid-19 pandemic there was a marked rise in the number of cardiovascular deaths. Obesity is a well-known modifiable risk factor for cardiovascular disease and has been identified as a factor which leads to poorer covid-19 related outcomes. In this study we aimed to analyse the impact of covid-19 on obesity-related cardiovascular deaths compared to trends seen 20 years prior. We also analysed the influence different demographics had on mortality. MethodsMultiple Cause of Mortality database was accessed through CDC WONDER to obtain the obesity-related and general cardiovascular crude mortality and age adjusted mortality rates (AMMR) between 1999 and 2020 in the US. The obesity-related sample was stratified by demographics and cardiovascular mortality was subdivided into ischemic heart disease, heart failure, hypertension and cerebrovascular disease. Joinpoint Regression Program (Version 4.9.1.0) was used to calculate the average annual percent change (AAPC) in AAMR, and hence projected AAMR. Excess mortality was calculated by comparing actual AAMR in 2020 to projected values. Results and discussionThere were an estimated 3058 excess deaths during the early stages of the pandemic impacting all cohorts. The greatest excess mortalities were seen in men, rural populations and in Asian/Pacific Islander and Native Americans. Interestingly the greatest overall mortality was seen in the Black American population. Our study highlights important, both pre and during the pandemic, in obesity related cardiovascular disease mortality which has important implications for ongoing public health measures.

Oral fast dissolving films for co-administration of breviscapine and matrine: Formulation optimization and in vitro characterization

Oral fast dissolving films (OFDFs) are popular dosage forms for enhanced oral absorption of active ingredients without experiencing gastrointestinal interference or first-pass metabolism. The primary challenge in OFDF design is balancing drug loading capacity with film properties, particularly for poorly soluble drugs. In the present work, an OFDF formulation containing co-amorphous mixture was successfully designed for co-administration of two natural products at a drug content of 14%. Breviscapine and matrine are commonly used for cardiovascular and cerebrovascular related diseases, but their clinical application was limited by low bioavailability, short biological half-life, and instability problems. Their co-administration as a compound remedy requires a novel product too enhance drug dissolution and patient compliance. A 33 Box-Behnken design was used to generate OFDF preparations by solvent casting method. The optimized blank film formulation, comprising 57.40% HPMC E50, 14.01% PEG 400 and 5.35% L-HPC, demonstrated a rapid disintegration in 18 s. XRD and FTIR analysis on drug-loaded films revealed good compatibility of drugs and polymers, and amorphous state of films with co-precipitates. The films were evaluated for morphology, folding endurance, disintegration time and in vitro BRE dissolution. Drugs incorporation extended the disintegration time of blank films, yet remained under 30 s. The co-amorphous mixture of BRE and MAT in films exhibited a faster BRE dissolution rate compared to the physical mixture. In conclusion, a compound OFDF formulation featuring a co-amorphous mixture of BRE and MAT offers an efficient strategy for hydrophobic drug delivery at high dose.

Zhilong Huoxue Tongyu capsule protects against atherosclerosis by suppressing EndMT via modulating Hippo/YAP signaling pathway

Background and aimZhilong Huoxue Tongyu Capsule (ZL capsule) has been demonstrated to be an effective and widely-used traditional Chinese medicine (TCM) formula for the treatment of various diseases, especially for atherosclerosis (AS) related cardiovascular and cerebrovascular diseases. Reversal of endothelial-mesenchymal transition (EndMT) plays a crucial role in the cure of AS. But the curative impact of ZL capsule on EndMT remains obscure during the development of AS. The purpose of this study is to explore the effect of ZL capsule on AS and to study the regulation mechanism on EndMT in AS by ZL capsule in vivo and in vitro. Experimental procedureAn in vivo model of AS was induced in ApoE−/− mice by administrating them with an 8-week period of high-fat diet (HFD). After oral gavage of different doses of ZL capsule and Atorvastatin calcium tablets (ATO) for 4 weeks, the lipid levels, plaque area, lipid deposition, and EndMT were evaluated using standard assays. In order to simulate EndMT in vitro, human umbilical vein endothelial cells (HUVECs) were subjected to oxidized low-density lipoprotein (ox-LDL). Western blotting (WB) and immunofluorescence techniques were used to evaluate the intervention effect of ZL capsule on EndMT and Hippo/YAP pathways. Results and conclusionZL capsule demonstrated therapeutic effects on dyslipidemia and EndMT among atherosclerotic mice. To be specific, ZL capusle diminished the total cholesterol (TC), total triglyceride (TG) and low-density lipoprotein (LDL-C) levels, whereas increased that of high-density lipoproteins (HDL-C). Meanwhile, ZL capusle upregulated the expression of endothelial markers (CD31 and VE-cadherin) and reduced that of mesenchymal markers (ɑ-SMA and FSP1), indicating that ZL capusle could inhibit EndMT during the development of AS. Furthermore, molecular docking results indicated that active ingredients including formononetin, calycosin, astragaloside III, astragaloside A in ZL capsule have strong affinity with YAP proteins, and ZL capsule can significantly repress the initiation of Hippo/YAP pathway during AS. In conclusion, ZL capsule effectively attenuated AS progression by exerting inhibitory effects on EndMT through modulation of the Hippo/YAP signaling pathway.

Reticulon 3 deficiency ameliorates post-myocardial infarction heart failure by alleviating mitochondrial dysfunction and inflammation.

Multiple molecular mechanisms are involved in the development of heart failure (HF) after myocardial infarction (MI). However, interventions targeting these pathological processes alone remain clinically ineffective. Therefore, it is essential to identify new therapeutic targets for alleviating cardiac dysfunction after MI. Here, gain- and loss-of-function approaches were used to investigate the role of reticulon 3 (RTN3) in HF after MI. We found that RTN3 was elevated in the myocardium of patients with HF and mice with MI. Cardiomyocyte-specific RTN3 overexpression decreased systolic function in mice under physiological conditions and exacerbated the development of HF induced by MI. Conversely, RTN3 knockout alleviated cardiac dysfunction after MI. Mechanistically, RTN3 bound and mediated heat shock protein beta-1 (HSPB1) translocation from the cytosol to the endoplasmic reticulum. The reduction of cytosolic HSPB1 was responsible for the elevation of TLR4, which impaired mitochondrial function and promoted inflammation through toll-like receptor 4 (TLR4)/peroxisome proliferator-activated receptor gamma coactivator-1 alpha(PGC-1α) and TLR4/Nuclear factor-kappa B(NFκB) pathways, respectively. Furthermore, the HSPB1 inhibitor reversed the protective effect of RTN3 knockout on MI. Additionally, elevated plasma RTN3 level is associated with decreased cardiac function in patients with acute MI. This study identified RTN3 as a critical driver of HF after MI and suggests targeting RTN3 as a promising therapeutic strategy for MI and related cardiovascular diseases.

Spatial Analysis Reveals Vascular Changes in Retinal and Choroidal Vessel Perfusion in Intermediate AMD With Reticular Pseudodrusen.

To examine the effect of reticular pseudodrusen (RPD) on retinal and choroidal vessel perfusion (VP) topography in intermediate age-related macular degeneration (iAMD) using refined spatial analyses. This was a retrospective cross-sectional study of 120 individuals with 30 iAMDRPD, 60 iAMDno_RPD, and 30 normal eyes, propensity-score matched by age, sex, and presence of cardiovascular-related disease. VP of the superficial and deep retinal and choriocapillaris vascular slabs was assessed from 6 × 6-mm optical coherence tomography angiography (OCTA) scans divided into 126 × 126 grids, with adjustment for various person- and eye-level factors. Grid-wise VP differences (%) among the groups were spatially assessed according to analyses based on the Early Treatment for Diabetic Retinopathy Study (ETDRS), eccentricity (µm), and degree (°). VP was significantly decreased between iAMDRPD and iAMDno_RPD, across all vascular slabs in various ETDRS sectors (up to -2.16%; 95% confidence interval, -2.99 to -1.34; P < 0.05). Eccentricity analyses revealed more complex patterns: a bisegmented relationship where VP in iAMDRPD eyes decreased linearly toward 1000µm then returned toward similar values as iAMDno_RPD, plateauing around 2000 µm in the superficial and 3000 µm in the deep retina (R2 = 0.57-0.9; P < 0.001). Degree-based analysis further showed that the greatest VP differences in iAMDRPD eyes were commonly located superiorly and nasally across all vascular slabs (P < 0.05). RPD appears to compound the vascular impact of iAMD, displaying complex spatial patterns beyond the ETDRS sectors. This highlights the importance of considering spatial delineations for future work regarding the role of RPD and vascular dysfunction.

The Effect and Mechanism of Oleanolic Acid in the Treatment of Metabolic Syndrome and Related Cardiovascular Diseases.

Metabolic syndromes (MetS) and related cardiovascular diseases (CVDs) pose a serious threat to human health. MetS are metabolic disorders characterized by obesity, dyslipidemia, and hypertension, which increase the risk of CVDs' initiation and development. Although there are many availabile drugs for treating MetS and related CVDs, some side effects also occur. Considering the low-level side effects, many natural products have been tried to treat MetS and CVDs. A five-cyclic triterpenoid natural product, oleanolic acid (OA), has been reported to have many pharmacologic actions such as anti-hypertension, anti-hyperlipidemia, and liver protection. OA has specific advantages in the treatment of MetS and CVDs. OA achieves therapeutic effects through a variety of pathways, attracting great interest and playing a vital role in the treatment of MetS and CVDs. Consequently, in this article, we aim to review the pharmacological actions and potential mechanisms of OA in treating MetS and related CVDs.

CLOP-hERG: The Contrastive Learning Optimized Pre-Trained Model for Representation Learning in Predicting Drug-Induced hERG Channel Blockers

During drug development, ensuring that drug molecules do not block the hERG (human Ether-à-go-go-Related Gene) channel is critical. If this channel is blocked, it can cause many cardiovascular-related diseases. However, traditional experimental detection methods are expensive and time-consuming. In this work, we proposed a novel deep learning framework CLOP-hERG, that combines contrastive learning with the RoBERTa pre-trained model to predict whether drug molecules will block the hERG channel. We employed data augmentation techniques on molecular structures to ensure that our model can capture the multifaceted information of the molecules. Besides, we used a contrastive learning strategy to enable the model to learn meaningful molecular features from large unlabeled datasets. The RoBERTa pre-trained model played a pivotal role in this process, giving our model with a robust representational learning capability. The model, obtained through contrastive learning, was further fine-tuned to achieve high-precision prediction of hERG blockers. Through a series of experiments, we demonstrated the effectiveness of CLOP-hERG. This work provides a novel and effective strategy for predicting hERG blockers and provides some insights for other similar pharmaceutical tasks.

Albumin Redox Modifications Promote Cell Calcification Reflecting the Impact of Oxidative Status on Aortic Valve Disease and Atherosclerosis.

Calcific aortic valve disease (CAVD) and coronary artery disease (CAD) are related cardiovascular diseases in which common mechanisms lead to tissue calcification. Oxidative stress plays a key role in these diseases and there is also evidence that the redox state of serum albumin exerts a significant influence on these conditions. To further explore this issue, we used multimarker scores (OxyScore and AntioxyScore) to assess the global oxidative status in patients with CAVD, with and without CAD, also evaluating their plasma thiol levels. In addition, valvular interstitial cells were treated with reduced, oxidized, and native albumin to study how this protein and its modifications affect cell calcification. The differences we found suggest that oxidative status is distinct in CAVD and CAD, with differences in redox markers and thiol levels. Importantly, the in vitro interstitial cell model revealed that modified albumin affects cell calcification, accelerating this process. Hence, we show here the importance of the redox system in the development of CAVD, emphasizing the relevance of multimarker scores, while also offering evidence of how the redox state of albumin influences vascular calcification. These data highlight the relevance of understanding the overall redox processes involved in these diseases, opening the door to new studies on antioxidants as potential therapies for these patients.

Fufang Zhenzhu Tiaozhi (FTZ) suppression of macrophage pyroptosis: Key to stabilizing rupture-prone plaques

BackgroundResearch on the Chinese herbal formula Fufang Zhenzhu Tiaozhi (FTZ) has demonstrated its effectiveness in treating hyperlipidemia and glycolipid metabolic disorders. Additionally, FTZ has shown inhibitory effects on oxidative stress, regulation of lipid metabolism, and reduction of inflammation in these conditions. However, the precise mechanisms through which FTZ modulates macrophage function in atherosclerosis remain incompletely understood. Therefore, this study aims to investigate whether FTZ can effectively stabilize rupture-prone plaques by suppressing macrophage pyroptosis and impeding the development of M1 macrophage polarization in ApoE−/− mice. MethodsTo assess the impact of FTZ on macrophage function and atherosclerosis in ApoE−/− mice, we orally administered FTZ at a dosage of 1.2 g/kg body weight daily for 14 weeks. Levels of interleukin-18 and interleukin-1β were quantified using ELISA kits to gauge FTZ's influence on inflammation. Total cholesterol content was measured with a Cholesterol Assay Kit to evaluate FTZ's effect on lipid metabolism. Aortic tissues were stained with Oil Red O, and immunohistochemistry techniques were applied to assess atherosclerotic lesions and plaque stability. To evaluate the effects of FTZ on macrophage pyroptosis and oxidative damage, immunofluorescence staining was utilized. Additionally, we conducted an analysis of protein and mRNA expression levels of NLRP3 inflammasome-related genes and macrophage polarization-related genes using RT-PCR and western blotting techniques. ResultsThis study illustrates the potential therapeutic effectiveness of FTZ in mitigating the severity of atherosclerosis and improving serum lipid profiles by inhibiting inflammation. The observed enhancements in atherosclerosis severity and inflammation can be attributed to the suppression of NLRP3 inflammasome activity and M1 polarization by FTZ. ConclusionThe current findings indicate that FTZ provides protection against atherosclerosis, positioning it as a promising candidate for novel therapies targeting atherosclerosis and related cardiovascular diseases.

Diabetic Vasculopathy: Molecular Mechanisms and Clinical Insights.

Clinical and basic studies have documented that both hyperglycemia and insulin-resistance/hyperinsulinemia not only constitute metabolic disorders contributing to cardiometabolic syndrome, but also predispose to diabetic vasculopathy, which refers to diabetes-mellitus-induced microvascular and macrovascular complications, including retinopathy, neuropathy, atherosclerosis, coronary artery disease, hypertension, and peripheral artery disease. The underlying molecular and cellular mechanisms include inappropriate activation of the renin angiotensin-aldosterone system, mitochondrial dysfunction, excessive oxidative stress, inflammation, dyslipidemia, and thrombosis. These abnormalities collectively promote metabolic disorders and further promote diabetic vasculopathy. Recent evidence has revealed that endothelial progenitor cell dysfunction, gut dysbiosis, and the abnormal release of extracellular vesicles and their carried microRNAs also contribute to the development and progression of diabetic vasculopathy. Therefore, clinical control and treatment of diabetes mellitus, as well as the development of novel therapeutic strategies are crucial in preventing cardiometabolic syndrome and related diabetic vasculopathy. The present review focuses on the relationship between insulin resistance and diabetes mellitus in diabetic vasculopathy and related cardiovascular disease, highlighting epidemiology and clinical characteristics, pathophysiology, and molecular mechanisms, as well as management strategies.

Consideraciones cardiovasculares para la práctica de buceo recreativo con escafandra autónoma. Documento de consenso de SEC-Asociación de Cardiología Clínica/SEC-GT Cardiología del Deporte

The practice of recreational scuba diving has increased worldwide, with millions of people taking part each year. The aquatic environment is a hostile setting that requires human physiology to adapt by undergoing a series of changes that stress the body. Therefore, physical fitness and control of cardiovascular risk factors are essential for practicing this sport. Medical assessment is not mandatory before participating in this sport and is only required when recommended by a health questionnaire designed for this purpose. However, due to the significance of cardiovascular disease, cardiology consultations are becoming more frequent. The aim of the present consensus document is to describe the cardiovascular physiological changes that occur during diving, focusing on related cardiovascular diseases, their management, and follow-up recommendations. The assessment and follow-up of individuals who practice diving with previous cardiovascular disease are also discussed. This document, endorsed by the Clinical Cardiology Association of the Spanish Society of Cardiology (SEC) and the SEC Working Group on Sports Cardiology of the Association of Preventive Cardiology, aims to assist both cardiologists in evaluating patients, as well as other specialists responsible for assessing individuals’ fitness for diving practice.