Endothelial dysfunction, which is characterized by damage to the endoplasmic reticulum (ER) and mitochondria, is involved in a variety of cardiovascular disorders. Here, we explored whether mitochondrial damage and ER stress are associated with endothelial dysfunction. We also examined whether and how melatonin protects against oxidized low‐density lipoprotein‐ (ox‐LDL‐) induced damage in endothelial cells. We found that CHOP, GRP78, and PERK expressions, which are indicative of ER stress, increased significantly in response to ox‐LDL treatment. ox‐LDL also induced mitochondrial dysfunction as evidenced by decreased mitochondrial membrane potential, increased mitochondrial ROS levels, and downregulation of mitochondrial protective factors. In addition, ox‐LDL inhibited antioxidative processes, as evidenced by decreased antioxidative enzyme activity and reduced Nrf2/HO‐1 expression. Melatonin clearly reduced ER stress and promoted mitochondrial function and antioxidative processes in the presence of ox‐LDL. Molecular investigation revealed that ox‐LDL activated the JNK/Mff signaling pathway, and melatonin blocked this effect. These results demonstrate that ox‐LDL induces ER stress and mitochondrial dysfunction and activates the JNK/Mff signaling pathway, thereby contributing to endothelial dysfunction. Moreover, melatonin inhibited JNK/Mff signaling and sustained ER homeostasis and mitochondrial function, thereby protecting endothelial cells against ox‐LDL‐induced damage.

Genome-wide association studies have shown that a disintegrin and metalloproteinase with thrombospondin motifs 9 (ADAMTS-9) is associated with the development of atherosclerosis. We assessed the level of ADAMTS-9 in patients with coronary artery disease (CAD) and its severity and prognosis. We selected 666 participants who underwent coronary angiography in our hospital and met the inclusion and exclusion criteria; participants included non-CAD patients, patients with stable angina pectoris (SAP), unstable angina, non-ST-segment elevation myocardial infarction, or ST-segment elevation myocardial infarction. The serum level of ADAMTS-9 was higher in patients with CAD than in non-CAD patients (37.53 ± 8.55 ng/mL vs 12.04 ± 7.02 ng/mL, P < .001) and was an independent predictor for CAD (odds ratio = 1.871, 95% CI: 1.533-2.283, P < .001). Subgroup analysis showed that compared with the SAP group, the acute coronary syndrome groups had higher serum levels of ADAMTS-9. In addition, the level of ADAMTS-9 was related to the SYNTAX score (r = 0.523, P < .001). Patients with acute myocardial infarction (AMI) with elevated levels of ADAMTS-9 had a higher risk of major adverse cardiovascular events (MACE) within 12 months than those with lower levels (log-rank = 4.490, P = .034). Plasma ADAMTS-9 levels may be useful for the diagnosis of CAD and as predictors of MACE in AMI patients.

Many studies have shown that leukocyte cell-derived chemotaxin 2 (LECT2) is associated with metabolic disorders, which is a risk factor of arteriosclerosis. We assessed the level of LECT-2 in patients with coronary artery disease (CAD) and its severity and prognosis. We selected 666 participants who underwent coronary angiography in our hospital and included patients with non-CAD, patients with stable angina pectoris (SAP), patients with unstable angina (UA), patients with non-ST-segment elevation myocardial infarction (NSTEMI) and patients with ST-segment elevation myocardial infarction (STEMI). The serum level of LECT-2 was higher in patients with CAD than in patients with non-CAD and was an independent predictor for CAD. Subgroup analysis showed that compared with the SAP group, the UA, NSTEMI, and STEMI groups had higher serum levels of LECT-2. In addition, the level of LECT-2 was related to the SYNTAX score and SYNTAX II score. Finally, patients with acute myocardial infarction (AMI) with elevated levels of LECT-2 had a higher risk of major adverse cardiovascular events (MACEs) within 12 months than those with lower levels of LECT-2. Plasma LECT-2 levels may be useful for the diagnosis of CAD and as predictors of MACE in patients with AMI.

Purpose: The Baolier capsule (BLEC) is a proprietary Mongolian medicine administered for treating hypercholesterolemia and atherosclerosis (AS). However, the therapeutic effects, primary bioactive ingredients, and potential mechanisms underlying hypercholesterolemia and AS remain unclear. This study aimed to investigate the pharmacological effects, principal active ingredients, and mechanisms of BLEC against hypercholesterolemia and AS. Methods: Adeno-associated virus tail vein injection was utilized to construct liver-specific LXRα knockout ApoE^−/− mice. A high-fat diet was utilized to feed ApoE^−/− mice to build hyperlipidemia and AS mouse models. The aorta or liver stained with Oil Red O was used to assess the effect of the drugs on AS or fatty liver formation after the oral administration of BLEC, piperine, statins, or ezetimibe to the mice following the experimental protocol. Biochemical assays were utilized to evaluate the effect of the drugs on serum lipid levels and cholesterol efflux indicators. Transcriptomics was employed to investigate the effect of BLEC on liver gene expression levels. HPLC-MS/MS was used to determine BLEC and its major components in the liver. Western blotting or quantitative reverse transcription polymerase chain reaction was conducted to detect LXRα, ABCA1, ABCG5, ABCG8, and CYP7A1 expression. Results: Here, we revealed that BLEC decreases lipid levels in the serum and liver, as well as decelerates AS by promoting cholesterol excretion. BLEC and piperine, which are the main components exposed in the target liver tissue, activate LXRα to upregulate ABCA1, ABCG5, ABCG8, and CYP7A1, which promotes cholesterol transport to high-density lipoprotein and excretion to bile and feces. Notably, piperines demonstrated synergistic beneficial effects with atorvastatin or ezetimibe, which are two widely used hypocholesterolemic and anti-atherosclerotic drugs. Conclusion: BLEC and its main active ingredient, piperine, promote cholesterol excretion, reduce serum cholesterol levels, inhibit AS, and exhibit good clinical application value and prospects.