Impact of Obesity on Microvascular Obstruction and Area at Risk in Patients After ST-Segment-Elevation Myocardial Infarction: A Magnetic Resonance Imaging Study.

Background: Better survival for overweight and obese patients after ST-segment elevation myocardial infarction (STEMI) has been demonstrated. The association between body mass index (BMI), microvascular obstruction (MVO), and area at risk (AAR) after STEMI was evaluated. Methods: A prospective observational study was performed to enrolled patients undergoing primary percutaneous coronary intervention (pPCI) for STEMI and cardiac magnetic resonance was performed within 5-7 days. Patients were classified as normal weight (18.5 ≤BMI <24.0 kg/m2), overweight (24.0 ≤BMI <28.0 kg/m2), or obese (BMI ≥28 kg/m2). Results: Among 225 patients undergoing pPCI, 67 (30.00%) were normal weight, 113 (50.22%) were overweight, and 45 (20.00%) were obese. BMI ≥28 kg/m2 was significantly associated with less risk of MVO when compared with a normal BMI after multivariable adjustment (overweight: HR 0.29, 95% CI 0.13-0.68, p = 0.004). Compared with normal weight patients, obese and overweight patients tend to have larger hearts (greater left ventricular end-diastolic volume [LVEDV] and left ventricular [LV] mass). In adjusted analysis, increased BMI was significantly associated with a smaller AAR. In addition, obese patients had a smaller AAR (ß = -0.252, 95% CI -20.298- -3.244, p = 0.007) and AAR, % LV mass (ß = -0.331, 95% CI -0.211- -0.062, p < 0.001) than normal weight patients. Conclusion: Obesity (BMI ≥28 kg/m2) is independently associated with lower risks of MVO and a smaller AAR, % LV mass than normal weight patients among subjects undergoing pPCI for STEMI.

Exosome-Mediated miR-155 Transfer from Smooth Muscle Cells to Endothelial Cells Induces Endothelial Injury and Promotes Atherosclerosis.

The vascular response to pro-atherosclerotic factors is a multifactorial process involving endothelial cells (ECs), macrophages (MACs), and smooth muscle cells (SMCs), although the mechanism by which these cell types communicate with each other in response to environmental cues is yet to be understood. Here, we show that miR-155, which is significantly expressed and secreted in Krüppel-like factor 5 (KLF5)-overexpressing vascular smooth muscle cells (VSMCs), is a potent regulator of endothelium barrier function through regulating endothelial targeting tight junction protein expression. VSMCs-derived exosomes mediate the transfer of KLF5-induced miR-155 from SMCs to ECs, which, in turn, destroys tight junctions and the integrity of endothelial barriers, leading to an increased endothelial permeability and enhanced atherosclerotic progression. Moreover, overexpression of miR-155 in ECs inhibits endothelial cell proliferation/migration and re-endothelialization in vitro and in vivo and thus increases vascular endothelial permeability. Blockage of the exosome-mediated transfer of miR-155 between these two cells may serve as a therapeutic target for atherosclerosis.

1, 25(OH)2D3-induced interaction of vitamin D receptor with p50 subunit of NF-κB suppresses the interaction between KLF5 and p50, contributing to inhibition of LPS-induced macrophage proliferation.

KLF5 and nuclear factor κB (NF-κB) regulate cell proliferation and inflammation. Vitamin D signaling through vitamin D receptor (VDR) exerts anti-proliferative and anti-inflammatory actions. However, an actual relationship between KLF5, NF-κB and VDR in the inflammation and proliferation of macrophages is still unclear. Here, we showed that LPS and proinflammatory cytokines stimulate KLF5 gene expression in macrophages, and that 1, 25(OH)2D3 suppresses LPS-induced KLF5 expression and cell proliferation via upregulation of VDR expression. Mechanistic studies suggested that KLF5 interacts with p50 subunit of NF-κB to cooperatively induce the expressions of positive cell cycle regulators cyclin B1 and Cdk1/Cdc2 in LPS-treated macrophages. Further studies revealed that 1, 25(OH)2D3-induced interaction of VDR with p50 decreases LPS-induced interaction of KLF5 with p50. Collectively, we identify a novel regulatory pathway in which 1, 25(OH)2D3 induces VDR expression and promotes VDR interaction with p50 subunit of NF-κB, which in turn attenuates the association of KLF5 with p50 subunit of NF-κB and thus exerts anti-inflammatory and anti-proliferative effects on macrophages.