Current vascular pharmacology最新文献

Statins play a significant role in the prevention of cardiovascular (CV) diseases (CVDs); however, non-adherence with statin treatment or statin intolerance (mainly attributed to muscleassociated side effects) is not uncommon. New agents such as bempedoic acid (BA) can provide more treatment options. BA is administered orally, once daily, at a dose of 180 mg in current clinical practice. It can decrease circulating low-density lipoprotein cholesterol (LDL-C) levels by nearly 30% as monotherapy or by 20% as an add-on to statins. CV outcome studies have shown that BA decreases major adverse CV event risk in patients with established CVD or high CV risk by 13%. When patients with high CV risk were analyzed alone, the risk reduction was 30%. Its side effects include a rise in serum uric acid levels and liver enzyme activity, whereas it does not increase diabetes risk as statins do. BA can be used as adjunctive therapy to statins in patients at high CV risk in whom lipid targets cannot be achieved or as an alternative to statins in patients with statin intolerance.

Background: Statins are the most prescribed lipid-lowering drugs worldwide. The associated adverse events, especially muscle symptoms, have been frequently reported despite their perceived safety. Three pharmacogenes, the solute carrier organic anion transporter family member 1B1 (SLCO1B1), ATP-binding cassette subfamily G member 2 (ABCG2), and cytochrome P450 2C9 (CYP2C9) are suggested as safety biomarkers for statins. The Clinical Pharmacogenomic Implementation Consortium (CPIC) issued clinical guidelines for statin use based on these three genes.

Objectives: The present study aimed to examine variants in these pharmacogenes to predict the safety of statin use among the Emirati population.

Methods: Analyzing 242 whole exome sequencing data at the three genes enabled the determination of the frequencies of the single nucleotide polymorphisms (SNPs), annotating the haplotypes and the predicted functions of their proteins.

Results: In our cohort, 29.8% and 5.4% had SLCO1B1 decreased and poor function, respectively. The high frequency warns of the possibility of significant side effects of some statins and the importance of pharmacogenomic testing. We found a low frequency (6%) of the ABCG2:rs2231142 variant, which indicates the low probability of Emirati patients being recommended against higher rosuvastatin doses compared with other populations with higher frequencies of this variant. In contrast, we found high frequencies of the functionally impaired CYP2C9 alleles, which makes fluvastatin a less favorable choice.

Conclusion: Among the sparse studies available, the present one demonstrates all SLCO1B1 and CYP2C9 function-impairing alleles among Emiratis. We highlighted how population-specific pharmacogenomic data can predict safer choices of statins, especially in understudied populations.

Background: Targeting gut dysbiosis to treat chronic diseases or to alleviate the symptoms is a new direction for medical adjuvant therapies. Recently, postbiotics have received considerable attention as they are non-viable probiotic preparations that confer various health benefits to the host without the safety problems associated with using live microbial cells.

Objective: The aim of the study is to obtain selenium (Se) and zinc (Zn) enriched Saccharomyces boulardii postbiotic biomass and to analyze its modulation effect because these minerals play an important role in reducing gut dysbiosis linked to cardiovascular (CV) diseases.

Method: The effect of the S. boulardii and Se/Zn enriched yeast postbiotics on CV microbial fingerprint was studied in vitro using the gastrointestinal system (GIS 1) and analyzed by microbiological, chemical, and qPCR methods.

Result: There was a 2.2 log CFU/mL increase in the total bacterial load after SeZn postbiotic treatment and in the qPCR counts of Firmicutes phyla for both treatments. Beneficial taxa, Bifidobacterium spp. and Lactobacillus spp., as well as Bacteroidesspp. were up to 1.5 log higher after mineral- enriched postbiotic application, while the acetic acid level increased.

Conclusion: These preliminary studies highlight the therapeutic potential of using Se/Zn enriched yeast postbiotics as adjuvants for clinical treatments of CV diseases.

There are more than 80 different tripartite motifs (TRIM) proteins within the E3 ubiquitin ligase subfamily, including proteins that regulate intracellular signaling, apoptosis, autophagy, proliferation, inflammation, and immunity through the ubiquitination of target proteins. Studies conducted in recent years have unraveled the importance of TRIM proteins in the pathophysiology of vascular diseases. In this review, we describe the effects of TRIM proteins on vascular endothelial cells, smooth muscle cells, heart, and lungs. In particular, we discuss the potential mechanisms by which TRIMs regulate diseases and shed light on the potential therapeutic applications of TRIMs.

Objective: To investigate the pharmacological effects and molecular mechanisms of lanthanum hydroxide(LH) on ectopic mineralization of soft tissue and abnormal bone in rats with acute kidney injury(AKI).

Methods: Wistar rats were modeled by 5/6 nephrectomy. After the operation, the rats were divided into different groups, the biochemical indexes of serum collected at different times. LH was administered by intragastric tube at doses of 0.4, 0.2, and 0.1g/kg, respectively. Rats were sacrificed in the 16th week after LH treatment. Observation of pathological changes in tissues were made by specific staining. Western Blot, Real-Time Quantitative PCR, and immunohistochemistry techniques were used to detect the impact on pathway-related proteins.

Results: Compared with the control group (no LH administered), the serum phosphate level of the LH group was significantly reduced (p<0.01), calcification of the thoracic aorta was reduced (p<0.05, p<0.01) (Serum biochemical tests before dosing and during drug treatment cycles), renal fibrosis was improved (p<0.01), nuclear entry of nuclear factor kappa-B (NF-κB) was reduced (p<0.01), and the expression of the smooth muscle protein 22α (SM22α) was significantly increased (p<0.01). The expression of osteogenic marker genes was decreased. In addition, compared with the controls, the receptor activator for nuclear factor-κB ligand/osteoprotegerin (RANKL/OPG) ratio of the femur in the model group was increased (p<0.05).

Conclusion: LH can inhibit the occurrence and development of vascular calcification and bone abnormalities in AKI rats by inhibiting the NF-κB and RANKL/OPG signaling pathways.

Background: There is a need to assess myocardial damage after radiofrequency ablation of the pulmonary veins (PV) for persistent atrial fibrillation (PAF) in elderly patients.

Objective: To evaluate oxidative stress, inflammatory response and myocardial damage in elderly patients with PAF after radiofrequency ablation of the PV.

Methods: High-sensitivity troponin T (hsTnT), malondialdehyde-modified low-density lipoprotein (MDA-LDL), acrolein (ACR), lipid hydroperoxide (LHP), toll-like receptor 4 (TLR4), soluble growth stimulation expressed gene 2 (sST2), angiotensin II (Ang II) and myocardial blood flow (MBF) were determined before ablation and at 1, 3 and 5 months after radiofrequency ablation.

Results: The levels of hsTnT, MDA-LDL, ACR, LHP, TLR4, sST2 and Ang II were increased 3 months after ablations compared with before ablation and 1 month after ablation, respectively (P<0.001); they were further increased at 5 months after ablation compared with the 1- and 3-month groups, respectively (P<0.001). MBF was decreased in the 3 months group after ablations compared with before ablation and 1-month after ablation, respectively (P<0.001), and was further decreased in 5-months after ablations compared with 1-month and 3-month groups, respectively (P<0.001). Patients with epicardial monopolar radiofrequency ablation had higher levels of hsTnT, MDA-LDL, ACR, LHP, TLR4, sST2, Ang II and lower MBF than patients with endocardial monopolar and bipolar radiofrequency ablations, respectively (P<0.001).

Conclusion: Monopolar radiofrequency ablation method could result in more myocardial injury than bipolar radiofrequency ablation. Oxidative stress and inflammatory response may be involved in cardiac radiofrequency ablation-induced myocardial injury, resulting in myocardial ischemia in elderly patients with PAF.

Classical risk factors for atherosclerosis also play a role in the pathogenesis of venous thromboembolism (VTE). Low-density lipoprotein cholesterol has prothrombotic and endothelium- deteriorating effects which are not limited to the arterial system. The association between hypercholesterolemia and VTE has been established, but the benefits of statins in the prevention of VTE assessed by observation studies seemed equivocal. The large, randomized trial Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) recorded the occurrence of VTE as a protocol-specified endpoint and reported a reduced incidence of VTE among subjects taking 20 mg of rosuvastatin daily vs placebo (hazard ratio 0.57; 95% confidence interval 0.37-0.86; p=0.007). Similar results were confirmed by meta-analyses of observation studies and randomized trials. Recently, a Mendelian randomization study that took the presence of gene variants coding for less efficient hydroxymethyl-glutaryl coenzyme A reductase activity as a proxy for statin treatment, confirmed a small, but significant negative association between the score of selected genetic polymorphisms and the incidence of VTE. However, since the protective effects of statins are limited, they should not be substituted for guideline-recommended VTE prophylaxis or anticoagulation treatment.

Background: Postoperative atrial fibrillation (POAF) is associated with poor outcomes, including hemodynamic instability, stroke, myocardial infarction, and death. In hemodynamic stable patients, the rhythm-control strategy is more advantageous than rate control. Current standard intravenous amiodarone administration has limited success and a delayed effect; the acute success rate is 44% (8-12 h to several days).

Purpose: The aim of this study was to evaluate the effectiveness of higher amiodarone loading dosage to restore sinus rhythm in patients with POAF after noncardiac surgery.

Methods: This is a prospective, randomized, controlled single-center study. The study included 39 patients with POAF, divided into group I (n=27) (intravenous 600 mg amiodarone loading dosage over 2 h and infusion of 50 mg/h over a 24-h period) and group II (n=12) (standard protocol; 300 mg of bolus intravenously in 30 min and infusion of 50 mg/h over a 24-h period). The primary endpoint of the study was a restoration of sinus rhythm at the 24th hour.

Results: Baseline clinical, laboratory and echocardiographic characteristics of both groups were similar. The patients with higher loading amiodarone dosage had earlier restoration of sinus rhythm (2.38 ± 1.41 vs 8.66 ± 2.87 h, respectively; p=0.015). There was no significant difference in achieving sinus rhythm at the 24th hour between both groups.

Conclusion: Higher loading amiodarone dosage increased early conversions to sinus rhythm compared with standard amiodarone protocol in patients with POAF.

Hypothyroidism and hyperthyroidism, both overt and subclinical, are associated with increased risk of cardiovascular morbidity and mortality. The association between thyroid-stimulating hormone levels and cardiovascular risk has been demonstrated in large epidemiological studies and meta-analyses and is now considered a U-shaped curve. Several pathophysiological mechanisms linking thyroid and cardiovascular disease are known; however, specific clinical complications of peripheral arterial disease as endpoints of clinical trials have not been adequately investigated. The potential mechanisms linking hypothyroidism and peripheral arterial disease are endothelial dysfunction, blood pressure changes, dyslipidemia, and low-grade systemic inflammation. The potential mechanisms linking hyperthyroidism and peripheral arterial disease are hyperdynamic circulation, elevated systolic blood pressure, hypercoagulability, and possibly increased arterial inflammation.