Current vascular pharmacology最新文献

Abdominal Aortic Aneurysm (AAA) is a life-threatening vascular disease. Despite advancements in understanding the pathogenesis of AAA, significant knowledge gaps persist. Recent evidence increasingly implicates mitochondrial dysfunction as a contributing factor that exacerbates AAA, inducing further expansion of aneurysm, rupture, and subsequent death. This review summarizes the latest research findings and theories associated with AAA pathogenesis, with a particular focus on mitochondrial dysfunction in AAA, including mitochondrial quality control, mitochondrial membrane potential, mitochondrial morphology, oxidation and antioxidation, normal functioning of the respiratory chain, mitochondrial mutations, and the regulation of other mitochondrial signaling pathways. Moreover, we highlight potential medical interventions based on regulating mitochondrial function for AAA treatment.

Background: Cardiac microvessels are significantly reduced in diabetic patients, which is accompanied by a significant increase in the incidence of diabetic cardiac complications and increased mortality. This study aimed to investigate the role and possible mechanism of sirtuin 1 (Sirt1) in microvascular endothelial cell injury in diabetic hearts.

Methods: Type 2 diabetes mouse models and cardiac microvascular endothelial cell (CMEC) cell models were established. Cardiac microvessel density (MVD) was detected using Platelet- Endothelial Cell Adhesion Molecule 1 (CD31) immunohistochemistry. Mitochondrial reactive oxygen species (ROS) was detected with MitoSOX and morphology was observed with mitochondrial staining. CMECs angiogenesis was evaluated via scratch and angiogenesis assays. We measured cell viability with a Cell Counting Kit (CCK)-8 assay and cell injury with lactate dehydrogenase (LDH) release assay. We assessed apoptosis using TUNEL staining, Caspase-3 activity, and Western blot.

Results: The decrease in Sirt1 protein expression was accompanied by a decrease in cardiac microvessel density in type 2 diabetic mice. After 48 h of treating the CMECs with high-glucose and palmitic acid, it was discovered that the expression of Sirt1 and dynamin-related protein 1 (Drp1) Ser637 phosphorylated protein decreased, while the expression of Cleaved Caspase-3 protein increased. Also, the angiogenesis ability of endothelial cells was decreased, while mitochondrial ROS and mitochondrial division were increased, which culminated in aggravated endothelial cell injury and increased endothelial cell apoptosis. Increased Sirt1 protein expression and function at the gene and drug levels alleviated excessive mitochondrial division, reduced apoptosis, and improved the function of CMECs by increasing the phosphorylation of Drp1 Ser637.

Conclusion: Under diabetic conditions, the Sirt1/Drp1 pathway reduces injury to CMECs by inhibiting excessive mitochondrial division.

Introduction: With the widespread use of the radial artery in catheterization procedures, radial artery spasm (RAS) is frequently considered an undesirable event. It is known that anxiety increases RAS, and listening to music helps individuals control anxiety during the procedure. This study aimed to investigate the effects of music concerts on RAS.

Methods: In this prospective study, imaging and interventional coronary catheterization procedures using the radial artery were included. One group listened to a musical recital during the procedure, while the other group was treated in a quiet environment. The demographics, procedural parameters, and complications of both groups were compared.

Results: The study included a total of 147 patients, with an average age of 51.6 ± 11.1 years. Of these, 78 patients (53%) listened to music, while 69 patients (46.9%) underwent catheterization in a quiet environment. The impact of music therapy on the RAS was found to be significant (11.5% vs. 20.3%; p=0.035). While music therapy showed a potential to reduce RAS rates, its effect was not statistically significant in multivariate analysis (p=0.055).

Conclusion: Music is a feasible, simple, and inexpensive method for reducing anxiety levels in patients. Listening to music during catheterization can reduce procedural discomfort and the frequency of undesirable events by helping people control their anxiety.

Hereditary Hemorrhagic Telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a rare and inherited vascular disorder characterized by the development of arteriovenous malformations (AVMs) in various organs and telangiectasia (small AVM) in the mucocutaneous. The majority of HHT patients have haploinsufficiency of genes involved in the transforming growth factor-beta (TGF-β) signaling pathway, including endoglin (ENG), activin receptor-like kinase 1 (ALK1, also known as ACVRL1), or SMAD4. Active angiogenesis is also required for telangiectasia and AVM development. Anti-angiogenic strategies have been tested in patients and animal models extensively. However, the exact mechanisms for telangiectasia and AVM development remain unclear. In this review, we discussed several important advances in the past 10 years in understanding HHT disease mechanisms and in therapeutic development.

With the aging population on the rise, the higher prevalence of atrial tachyarrhythmia is emerging as a significant healthcare concern. Atrial fibrillation (AF) stands out as the most common atrial tachyarrhythmia, potentially leading to adverse outcomes, such as stroke, heart failure (HF), or conduction dysfunction. Furthermore, AF may serve as a manifestation of underlying atrial cardiomyopathy, which forms the structural and electrical substrate for arrhythmias. Atrial cardiomyopathy is characterized by structural and electrical remodeling of the atria, resulting in impaired mechanical function and the generation of arrhythmias. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have recently emerged as a novel medical treatment for HF. Their use has been associated with a reduced incidence of new-onset AF, potentially attributing to the improvement of atrial cardiomyopathy. This effect is achieved through the regulation of glucose utilization and energy consumption within the myocardium. It is worth noting that the sirtuin signaling pathway plays a crucial role in regulating energy consumption, especially in the presence of increased oxidative stress and fibrosis. This pathway also exerts a significant influence on various cardiovascular diseases. This review aims to provide a comprehensive summary of the involvement of the sirtuin signaling pathway in cardiovascular diseases, with a specific focus on atrial cardiomyopathy and AF and the potential molecular mechanisms of SGLT2is in the sirtuin signaling pathway and atrial cardiomyopathy.

Introduction: This study aimed to investigate the factors influencing medication adherence in community-dwelling Chinese older adults with hypertension.

Design: Empirical research-quantitative; Cross-sectional study Methods: A cross-sectional survey was conducted from September to December 2021, in which participants completed a self-administered questionnaire with detailed their demographic information. The Morisky Medication Adherence Scale-8, the Pittsburgh Sleep Quality Index, and the 10-item Kessler Psychological Distress Scale were used to assess medication adherence, sleep quality, and psychological well-being, respectively. Multivariate logistic regression analysis was performed with medication adherence as the dependent variable to identify factors influencing adherence.

Results: The study included 867 patients with hypertension, comprising 566 women and 301 men with a mean age of 70.89 ± 7.50 years. Results indicated that 53.9% of participants exhibited high medication adherence, while 24.5% and 21.7% demonstrated medium and low adherence levels, respectively. Multiple logistic regression analysis revealed that individuals in the 50-59 age group had lower medication adherence compared to those aged 80 years and older (odds ratio [OR]: 0.468, 95% confidence interval [CI]: 0.245,0.894). In addition, participants with a primary school education or less (OR: 0.152, 95% CI: 0.095,0.245) and those living alone (OR: 0.362, 95% CI: 0.228, 0.575) exhibited poorer medication adherence. Conversely, living in an urban area was associated with better adherence (OR: 2.131, 95% CI: 1.402, 3.239, p < 0.001).

Conclusion: Our study showed that participants' medication adherence was below the desired level. It was observed that older adults, those with a junior high school education or higher, and those living in urban areas with their children had better medication adherence. These identified predictors may help to identify individuals at high risk of poor adherence, enabling the implementation of effective interventions to reduce the global burden of hypertension.

Resveratrol [RES] is a polyphenolic stilbene with therapeutic potential owing to its antioxidant, anti-inflammatory, neuroprotective, and cardioprotective properties. However, the very poor oral bioavailability, fast metabolism, and extremely low stability under physiological conditions pose a severe detriment to the clinical use of RES. This newly developed field of nanotechnology has led to the formulation of RES into nanoformulations with the goal of overcoming metabolicpharmacokinetic limitations and enhancing the targeted transport of RES to the central nervous system [CNS]. Among the various routes of administration, the combination of nose-to-brain [N2B] delivery via the intranasal [IN] route has recently garnered attention as a straightforward, noninvasive route for transport to the blood-brain barrier [BBB] for greater effects and less harmful systemic side effects by transporting nano-encapsulated RES into the neural tissues. This review critically summarizes the mechanisms and benefits of the N2B route for the delivery of RES nanoformulations, collating in vivo data demonstrating increased CNS bioavailability and stability and, consequently, improved therapeutic efficacy in animal models of neurodegenerative diseases. Compared with the more 'traditional' routes of administration, IN administration of RES nanoformulations is less toxic, cost-effective, and efficient in crossing the BBB. Therefore, this route represents a promising approach to the management of CNS disorders. Further optimization of nanoformulation design and clinical protocols is required to translate these promising findings into therapeutic strategies aimed at neuroprotection and disease modification in human CNS pathologies.

Purpose: The objective of this study was to explore the relationship among serum levels of the growth-stimulating expressed gene 2 protein (ST2), Galectin-3(GAL-3), N-terminal pro-B-type natriuretic peptide (NT-proBNP) in elderly hypertensive patients and heart failure with preserved ejection fraction (HFpEF).

Materials and methods: Eighty-five elderly hypertensive patients with HFpEF were registered as the HFpEF group, and 46 hypertensive patients without HF were registered as the Non-HF group. The levels of serum sST2 (soluble ST2), Galectin-3, and NT-proBNP were measured, and related indexes of heart function were performed with echocardiography in two groups, respectively.The obtained variables were applied to statistical software for analysis.

Results: Age, BMI, SBP, DBP, TC, LDL-C, HCY, sST2, Galectin-3, NT- proBNP, LVEDD, IVSD, LVEF, and E/A were obviously different between the two groups (p < 0.05). The levels of sST2, Galectin- 3 and NT- proBNP in the HFpEF group were higher than in the Non-HF group (P < 0.05). ANOVA results indicated that sST2, Galectin-3, and NT- proBNP levels increased gradually with the increasing NYHA grades (P<0.05). BMI, SBP, DBP, TC, LDL-C, FBG,UA, HCY, LVEDD, IVSD, LVEF, and E/A were significant differences in patients with different NYHA classes (P < 0.05). Spearman indicated that sST2, Galectin-3, and NT-proBNP were positively correlated with BMI, SDP, DBP, LDL-C, FBG, and HCY (P < 0.05). Logistic analysis indicated that BMI, SBP, DBP, FBG, HCY,sST2, Galectin-3, NT-proBNP, LVEDD, LVEF, and E/A were risk factors for hypertension with HFpEF. (P < 0.05). ROC indicated that the AUC of the diagnostic performance of sST2, Galectin-3, and NT-proBNP were all above 0.7, which may have some forecasting value for elderly hypertensive patients with HFpEF.

Conclusion: The levels of sST2, Galectin-3, and NT-proBNP were closely related to cardiac function grades. sST2, Galectin-3, and NT-proBNP have similar diagnostic performance and predictive value for elderly hypertensive patients with HFpEF. sST2 was more sensitive than NT-proBNP. It is recommended that measurements of sST2, Galectin-3 and NT-proBNP levels in elderly hypertensive patients may be useful in classifying early HFpEF.

Background: Among the organ damage mediated by hypertension, cardiac lesions hold significant importance. Numerous authors focus on hypertensive heart disease (HHD) rather than exclusively on left ventricular hypertrophy (LVH).

Objective: This narrative review aims to assess the incorporation of the concept of 'hypertensive heart disease' (HHD) in hypertension (HTN) guidelines. Furthermore, if HHD is not addressed, the review will evaluate the potential benefits of including this concept in future studies.

Methods: The following databases were searched: Scopus, Medline, Springer, Science Direct, Wiley, SAGE, Cambridge, Oxford Journals, and Google Scholar. Attention was given to the guidelines related to hypertension(HTN); the search items were "guidelines" and "hypertension." Within these guidelines, we specifically sought references to 'hypertensive heart disease.'.

Results: The concept of "HHD" is clearly advantageous compared to "HTN LVH," as it not only addresses LVH but also considers other structures of the heart that may be severely affected, which can significantly influence treatment. The concept of "hypertensive heart disease" is mentioned in only 8 out of 36 guidelines on HTN. The therapeutic implications and recommendations are absent in the guidelines.

Conclusion: The concept of HHD is reasonable and evidence-based, and there is no reason to focus only on LVH when considering HTN-induced damage to the heart. It is time to update our recommendations for heart treatment by using the phrase "Treatment of hypertensive heart disease" instead of "Treatment of hypertensive LVH." This update can enhance our awareness of the need to improve not only HTN LVH but the other parts of the heart as well.

Purpose: The management of acute heart failure (AHF) is crucial and challenging. Regarding the use of inotropes, correct patient selection and time of administration are of the essence. We hypothesize that the early use of Levosimendan favouring hemodynamic stabilization and enables rapid optimization of guideline-directed medical treatment (GDMT) in patients with HF, eventually impacting the patient's prognosis during the vulnerable phase.

Methods: This prospective, observational study enrolled consecutive patients admitted due to AHF. Propensity score matching (PSM) analysis has been used to homogenize differences between groups. In group 1 (G1), patients were treated with early 24-h Levosimendan infusion followed by in-hospital introduction/up-titration of GDMT. In group 2 (G2), patients were treated with alternative inotropes/ vasopressors followed by in-hospital introduction/up-titration of GDMT. The comparison between the two groups has been performed at the 6-month follow-up in terms of cardiovascular (CV) mortality and HF hospitalizations (HFH).

Results: 233 patients were included in the present study, and after propensity match adjustments, 176 patients were analysed, 88 patients for each group. No differences in the baseline characteristics have been reported between the groups. At 6 months follow-up, no statistically significant differences were shown in terms of the composite endpoint of CV death and HFH (p= 0.445) and CV death (p=0.62). Statistically significant differences between the two groups were reported in terms of HFH (p= 0.02). The Kaplan-Meier survival analysis showed that patients in G1 were significantly less hospitalized compared to G2 during the 6 months after the index hospitalization (log-rank p= 0.03).

Conclusions: Early 24-hour infusion of Levosimendan followed by rapid optimization of HF diseasemodifying therapies results in a significant reduction of HFH in the vulnerable post-discharge phase.