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Ca v 3.1 T-type calcium channel blocker reduces atherosclerosis by increasing cholesterol efflux and inhibition of lipid accumulation through p38/JNK-LXRα-ABCA1/ABCG1 signaling pathways. [Display omitted] Calcium channel blockers (CCBs) are commonly used as antihypertensive agents. While certain L-type CCBs exhibit antiatherogenic effects, the impact of Ca v 3.1 T-type CCBs on antiatherogenesis and lipid metabolism remains unexplored. NNC 55–0396 (NNC) is a highly selective blocker of T-type calcium channels (Ca v 3.1 channels). We investigated the effects of NNC on relevant molecules and molecular mechanisms in human THP-1 macrophages. Cholesterol efflux, an indicator of reverse cholesterol transport (RCT) efficiency, was assessed using [3H]-labeled cholesterol. In vivo, high cholesterol diet (HCD)-fed LDL receptor knockout (Ldlr -/-) mice, an atherosclerosis-prone model, underwent histochemical staining to analyze plaque burden. Treatment of THP-1 macrophages with NNC facilitated cholesterol efflux and reduced intracellular cholesterol accumulation. Pharmacological and genetic interventions demonstrated that NNC treatment or Ca v 3.1 knockdown significantly enhanced the protein expression of scavenger receptor B1 (SR-B1), ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), and liver X receptor alpha (LXRα) transcription factor. Mechanistic analysis revealed that NNC activates p38 and c-Jun N-terminal kinase (JNK) phosphorylation, leading to increased expression of ABCA1, ABCG1, and LXRα-without involving the microRNA pathway. LXRα is required for NNC–induced ABCA1 and ABCG1 expression. Administering NNC diminished atherosclerotic lesion area and lipid deposition in HCD-fed Ldlr -/- mice. NNC's anti-atherosclerotic effects, achieved through enhanced cholesterol efflux and inhibition of lipid accumulation, suggest a promising therapeutic approach for hypertensive patients with atherosclerosis. This research highlights the potential of Ca v 3.1 T-type CCBs in addressing cardiovascular complications associated with hypertension. [ABSTRACT FROM AUTHOR]

Background: Left ventricular assist devices (LVADs) have been used as an effective therapeutic option in patients with advanced heart failure, either as a bridge to transplantation, as destination therapy, or in some patients, as a bridge to recovery.Objectives: This study evaluated whether patients undergoing an LVAD bridge-to-recovery protocol can achieve cardiac and physical functional capacities equivalent to those of healthy controls.Methods: Fifty-eight male patients-18 implanted with a continuous-flow LVAD, 16 patients with LVAD explanted (recovered patients), and 24 heart transplant candidates (HTx)-and 97 healthy controls performed a maximal graded cardiopulmonary exercise test with continuous measurements of respiratory gas exchange and noninvasive (rebreathing) hemodynamic data. Cardiac function was represented by peak exercise cardiac power output (mean arterial blood pressure × cardiac output) and functional capacity by peak exercise O2 consumption.Results: All patients demonstrated a significant exertional effort as demonstrated with the mean peak exercise respiratory exchange ratio >1.10. Peak exercise cardiac power output was significantly higher in healthy controls and explanted LVAD patients compared with other patients (healthy 5.35 ± 0.95 W; explanted 3.45 ± 0.72 W; LVAD implanted 2.37 ± 0.68 W; and HTx 1.31 ± 0.31 W; p < 0.05), as was peak O2 consumption (healthy 36.4 ± 10.3 ml/kg/min; explanted 29.8 ± 5.9 ml/kg/min; implanted 20.5 ± 4.3 ml/kg/min; and HTx 12.0 ± 2.2 ml/kg/min; p < 0.05). In the LVAD explanted group, 38% of the patients achieved peak cardiac power output and 69% achieved peak O2 consumption within the ranges of healthy controls.Conclusions: The authors have shown that a substantial number of patients who recovered sufficiently to allow explantation of their LVAD can even achieve cardiac and physical functional capacities nearly equivalent to those of healthy controls. [ABSTRACT FROM AUTHOR]

Abstract: The implantable venous port system has gained popularity as venous access when prolonged chemotherapy is needed in cancer patients. Intravascular fracture and embolization of catheter fragments from port-catheter systems is rare. Here we report a 49-year-old lady who was found having a fractured port-catheter located over the right ventricular outflow tract (RVOT). Percutaneous transfemoral transcatheter retrieval of the fractured catheter was performed but complicated with flailed tricuspid valve. [Copyright &y& Elsevier]