Current vascular pharmacology最新文献

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: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as a groundbreaking class of antidiabetic medications renowned for their glucose-lowering effects and cardiovascular benefits. Recent studies have suggested that SGLT2 inhibitors may extend their influence beyond glycemic control to impact adipose tissue physiology, particularly within the epicardial adipose depot. Epicardial adipose tissue (EAT), an actively secretory organ surrounding the heart, has been implicated in the modulation of cardiovascular risk.

Aims: This systematic review and meta-analysis aims to systematically review and synthesize existing literature on the effects of SGLT2 inhibitors on EAT.

Methods: We performed a literature search for studies assessing the changes in epicardial adipose tissue volume/thickness before and after treatment with an SGLT2 inhibitor. We excluded reviews, editorials, case reports/case series, experimental studies, and studies that did not use SGLT2 inhibitors as the intervention. The main outcome of interest was the change in EAT volume/thickness at follow-up.

Results: The literature search yielded 72 results. After the application of the exclusion criteria, a total of 11 studies were selected for data extraction and inclusion in the meta-analysis. A mean of 6.57ml decreased EAT volume, and EAT thickness was reduced by a mean of 1.55mm. We detected that treatment with an SGLT2 inhibitor was associated with decreased EAT volume/thickness compared to the control group (SMD -1.79, 95% CI -2.91 to -0.66, p<0.01). There was substantial betweenstudy heterogeneity (I2: 94%, p<0.001). Results remained robust even after the exclusion of any single study. Subgroup analysis revealed a significantly greater effect size in randomized studies. Funnel plot inspection and Egger's regression test did not indicate the presence of publication bias.

Conclusion: This meta-analysis suggests that SGLT2 inhibitors use is associated with a reduction in EAT volume/thickness, posing as a potential mechanism of their beneficial effects in heart failure (HF) outcomes.

Background: Contrast-induced Acute Kidney Injury (CI-AKI) frequently occurs as a complication following PCI, making the identification of high-risk patients challenging. While the systemic immune inflammation index (SII) might aid in predicting CI-AKI, the current evidence remains insufficient.

Methods: We conducted a systematic literature search using PubMed, Web of Science, Embase, and the Cochrane Library, with a cut-off date of 3/20/2024. We included observational studies that examined the predictive value of SII for the risk of CI-AKI.

Results: This meta-analysis encompassed 8 studies with a combined total of 6301 participants. Results showed pooled sensitivity and specificity of 0.73 (95% CI 0.69-0.76) and 0.68 (95% CI 0.57- 0.77), respectively. The sROC curve analysis indicated an AUC of 0.74 (95% CI 0.70-0.78). The risk of publication bias was low (p = 0.18).

Conclusion: The results of this study suggest that SII has a relatively high sensitivity and could function as a biomarker for the prediction of CI-AKI risk in people receiving PCI treatment.

Diabetic foot ulcers (DFUs) pose a significant clinical challenge, characterized by impaired wound healing, chronic inflammation, and increased risk of infection. Neutrophils, as critical components of the innate immune response, play a pivotal role in the initial stages of wound healing, particularly during the inflammatory phase. This review explores the intricate relationship between neutrophil migration, inflammation, and the pathogenesis of DFU and drugs that can impact neutrophil production and migration. Neutrophils contribute to infection control through phagocytosis and release pro-inflammatory cytokines and reactive oxygen species, which, when dysregulated, can impede the wound healing process. Furthermore, the chronic hyperglycemic state characteristic of diabetes mellitus has been implicated in impairing neutrophil functions, including chemotaxis and oxidative burst. This compromised neutrophil response prolongs the inflammatory phase and disrupts the delicate balance required for efficient wound healing. Neutrophil extracellular traps (NETs), a unique form of neutrophil defence, have also been implicated in DFU pathogenesis, potentially exacerbating inflammation and tissue damage. Understanding the intricate interplay between neutrophil migration, dysregulated inflammatory responses, and hyperglycemia-driven impairments is essential for developing targeted therapeutic strategies for DFUs. This review sheds light on the critical role of neutrophils in DFU pathogenesis, and innovative and advanced treatment strategies for DFU, highlighting the potential for novel interventions to restore the balance between pro-inflammatory and wound healing processes, ultimately improving clinical outcomes for individuals with DFU.

Introduction/objective: The influence of cognitive behavioral therapy (CBT) and its modalities on various neuropsychiatric conditions is herein explored together with their impact on specific cardiovascular (CV) diseases (CVD).

Methods: A comprehensive review of the literature was undertaken via the PubMed, Scopus and Google Scholar on the above relevant topics. The focus was on large randomized controlled trials and meta-analyses.

Results: Among the various neuropsychiatric disorders, depression and anxiety commonly occur in CVD patients, frequently eluding clinician's attention. This reciprocal liaison may incur higher rates of morbidity/mortality, through physiological and behavioral mechanisms. Multimodal psychiatric interventions, using medications and psychotherapies, such as CBT, seem promising. Such mindfulness-based interventions have the potential to be an efficacious complementary strategy to address psychological stress in CVD patients. As the cost of CBT is relatively low, such a supportive approach for stress management provides high patient acceptability, with a positive impact on improving quality of life, by promoting CV health and mitigating CV complications.

Conclusion: There is ample evidence of a reciprocal liaison between heart and mind. Several CV risk factors are strongly affected by diseases of the mind, and the clinical course of various CVDs is influenced by affective or other psychiatric disorders. CBT and relevant mindfulness-based interventions have a significant supportive role in patients with various CVDs by targeting CV risk factor(s) or the underlying specific CVD and by identifying and addressing psychosocial issues. In this direction, various CBT interventions can provide the means to favorably influence both CV risk factors and CVDs.