Remote ischaemic preconditioning (RIPC) is well known to protect the myocardium against ischaemia/reperfusion injury (IRI). Exosomes are small extracellular vesicles that have become the key mediators of intercellular communication. Various studies have confirmed that circulating exosomes mediate RIPC. However, the underlying mechanisms for RIPC-induced exosome-mediated cardioprotection remain elusive. In our study, we found that the expression level of miR-24 was higher in exosomes derived from the plasma of rats subjected to RIPC than in exosomes derived from the plasma of control rats in vivo. The rat plasma exosomes could be taken up by H9c2 cells. In addition, miR-24 was present in RIPC-induced exosomes and played a role in reducing oxidative stress-mediated injury and decreasing apoptosis by downregulating Bim expression in H2O2-treated H9c2 cells in vitro. In vivo, miR-24 in RIPC-induced exosomes reduced cardiomyocyte apoptosis, attenuated the infarct size and improved heart function. Furthermore, the apoptosis-reducing effect of miR-24 was counteracted by miR-24 antagomirs or inhibitors both in vitro and in vivo. Therefore, we provided evidence that RIPC-induced exosomes could reduce apoptosis by transferring miR-24 in a paracrine manner and that miR-24 in the exosomes plays a central role in mediating the protective effects of RIPC.

Arterial stiffness plays a key role in the pathogenesis of cardiovascular disease. However, the relationship between lipid levels and arterial stiffness is controversial. We aimed to investigate the association between lipid parameters and brachial-ankle pulse-wave velocity (baPWV) in Chinese patients with hypertension. A total of 14 071 participants with hypertension in the China Stroke Primary Prevention Trial (CSPPT) were enrolled in the present study. Patients were assigned to 4 equal groups according to their baPWV. Participants in the highest baPWV group were older with a higher prevalence of stroke and diabetes mellitus as well as higher body mass index (BMI), blood pressure, fasting plasma glucose, uric acid, total cholesterol (TC), triglycerides (TG), homocysteine (Hcy), and vitamin B12 levels (P < .001). After adjusting for age, sex, BMI, and other cardiovascular risks, highdensity lipoprotein cholesterol (HDL-C) was negatively related to baPWV (b ¼ À0.22, P ¼ .012), TC (b ¼ 0.08, P ¼ 0.001), TG (b ¼ 0.14, P ¼ .001); non-HDL-C (b ¼ 0.12, P ¼ .001) and positively related to baPWV. The effect was not observed for lowdensity lipoprotein cholesterol (LDL-C; b ¼ 0.12, P ¼ .335).These results suggested that non-HDL-C, TG, and TC were associated with arterial stiffness in a Chinese population with hypertension. HDL-C was inversely associated with arterial stiffness.

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The induction of mitochondrial reactive oxygen species (mtROS) by hyperglycemia is a key event responsible for endothelial activation and injury. Heat shock protein 22 (HSP22) is a stress-inducible protein associated with cytoprotection and apoptosis inhibition. However, whether HSP22 prevents hyperglycemia-induced vascular endothelial injury remains unclear. Here, we investigated whether HSP22 protects the vascular endothelium from hyperglycemia-induced injury by reducing mtROS production. We used a high-fat diet and streptozotocin injection model to induce type 2 diabetes mellitus (T2DM, metabolic syndrome) and exposed human umbilical vein endothelial cells (HUVECs) to high glucose following overexpression or silencing of HSP22 to explore the role of HSP22. We found that HSP22 markedly inhibited endothelial cell activation and vascular lesions by inhibiting endothelial adhesion and decreasing cytokine secretion. We performed confocal microscopy and flow cytometry assays using HUVECs and showed that HSP22 attenuated mtROS and mitochondrial dysfunction in hyperglycemia-stimulated endothelial cells. Mechanistically, using the mtROS inhibitor MitoTEMPO, we demonstrated that HSP22 suppressed endothelial activation and injury by eliminating hyperglycemia-mediated increases in mtROS. Furthermore, we found that HSP22 maintained the balance of mitochondrial fusion and fission by mitigating mtROS in vitro. HSP22 attenuated the development of vascular lesions by suppressing mtROS-mediated endothelial activation in a T2DM mouse model. This study provides evidence that HSP22 may be a promising therapeutic target for vascular complications in T2DM.