Current Vascular Pharmacology - Volume 22, Issue 2, 2024

Large bore accesses refer to accesses with a diameter of 10 French or greater and are necessary for various medical devices, including those used in transcatheter aortic valve replacement, endovascular aneurysm repair stent-grafts, and percutaneous mechanical support devices. Notably, the utilization of these devices via femoral access is steadily increasing due to advancements in technology and implantation techniques, which are expanding the pool of patients suitable for percutaneous procedures. However, procedures involving large bore devices carry a high risk of bleeding and vascular complications (VCs), impacting both morbidity and long-term mortality. In this review article, we will first discuss the incidence, determinants, and prognostic impact of VCs in patients undergoing large bore access procedures. Subsequently, we will explore the strategies developed in recent years to minimize VCs, including techniques for optimizing vascular puncture through femoral cannulation, such as the use of echo-guided access cannulation and fluoroscopic guidance. Additionally, we will evaluate existing vascular closure devices designed for large bore devices. Finally, we will consider new pharmacological strategies aimed at reducing the risk of periprocedural access-related bleeding.

Primary hyperparathyroidism (PHPT) is presented in various forms, including classic PHPT, characterised by increased parathyroid hormone (PTH) secretion, normohormonal PHPT, and normocalcaemic PHPT. Secondary hyperparathyroidism is characterised by increased PTH secretion triggered by factors such as vitamin D deficiency and kidney failure. This review aims to discuss the involvement of hyperparathyroidism (HPT) in atherosclerosis, including peripheral arterial disease (PAD). The increased level of PTH is involved in developing subclinical and overt vascular diseases, encompassing endothelial dysfunction, vascular stiffness, hypertension, and coronary and peripheral arterial diseases. It has been consistently associated with an augmented risk of cardiovascular morbidity and mortality, independent of classical risk factors for atherosclerosis. Chronic hypercalcemia associated with increased levels of PTH contributes to the development of calcification of vessel walls and atherosclerotic plaques. Vascular calcification can occur in the intima or media of the arterial wall and is associated with stiffness of peripheral arteries, which the formation of atherosclerotic plaques and narrowing of the vessel lumen can follow. For treating hyperparathyroidism, particularly SHPT, calcimimetics, novel phosphorus binders and novel vitamin D receptor activators are used. However, they are ineffective in severe PHPT. Therefore, parathyroidectomy remains the primary therapeutic option of PHPT.

The ribonucleic acid (RNA)-binding protein Cytoplasmic Polyadenylation Element Binding Protein 1 (CPEB1), a key member of the CPEB family, is essential in controlling gene expression involved in both healthy physiological and pathological processes. CPEB1 can bind to the 3'- untranslated regions (UTR) of substrate messenger ribonucleic acid (mRNA) and regulate its translation. There is increasing evidence that CPEB1 is closely related to the pathological basis of atherosclerosis. According to recent investigations, many pathological processes, including inflammation, lipid metabolism, endothelial dysfunction, angiogenesis, oxidative stress, cellular senescence, apoptosis, and insulin resistance, are regulated by CPEB1. This review considers the prevention and treatment of atherosclerotic heart disease in relation to the evolution of the physiological function of CPEB1, recent research breakthroughs, and the potential participation of CPEB1 in atherosclerosis.

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes Coronavirus disease 2019 (COVID-19), characterized by pulmonary infection ranging from asymptomatic forms to respiratory insufficiency and death. Evidence of cardiac involvement in COVID-19 is increasing, and systemic inflammation or direct heart damage by SARS-CoV-2 can prolong the corrected QT interval (QTc). Methods: In this observational study, a total of 333 consecutive patients admitted to the Covid Center of Verona University Hospital from November 2020 to April 2021 were included. Patients with bundle branch block, pacemaker-controlled heart rhythm and heart rate >120 beats/min were excluded. A complete electrocardiogram (ECG) was performed at admission, and QTc values of ≥440 ms for males and ≥460 ms for females were considered prolonged. Results: Overall, 153 patients had prolonged QTc (45.5%). In multivariate logistic regression analysis, male sex (odds ratio (OR)=6.612, p=0.046), troponin (OR=1.04, p=0.015) and lymphocyte count (OR=3.047, p=0.019) were independently associated with QTc prolongation. Multivariate logistic regression showed that QTc was independently associated with mortality (OR=4.598, p=0.036). Age, sex, the ratio between the partial pressure of oxygen (PaO2) and the fraction of inspired oxygen (FiO2) (P/F), and fibrosis-4 index for liver fibrosis (FIB-4) were also independently associated with mortality. Conclusion: QTc interval prolongation appears to be a frequent finding in patients with COVID-19. Moreover, prolonged QTc may be predictive of more severe forms of COVID-19 and worse outcome.

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.