Acute coronary syndrome (ACS) is a major cause of acute death worldwide. Both innate and adaptive immunity regulate atherosclerosis progression, plaque stability, and thrombus formation. Immune and inflammation dysfunction have been indicated in the pathogenesis of ACS. The imbalance in the proatherogenic and antiatherogenic immune networks promotes the transition of plaques from a stable to unstable state and results in the occurrence of acute coronary events. The residual inflammatory risk (RIR) has received increasing attention in recent years, and lowering RIR has been expected to improve the outcomes of ACS patients. The CANTOS, COLCOT, and LoDoCo trials verified the benefits of reducing cardiovascular events using anti‐inflammation therapies; however, most of the other studies focusing on lowering RIR produced negative or contradicting results. Therefore, restoring the balance in autoimmune regulation is essential because proatherogenic and antiatherogenic immunomodulatory effects are equally important in the complex human immune network. In this review, we summarized the recent evidence of the roles of proatherogenic and antiatherogenic immune networks in the pathogenesis of ACS and discussed how immune and inflammation contribute to atherosclerosis progression, plaque instability, and adverse cardiovascular events. We also provide a “from bench to bedside” perspective of a novel and promising personalized strategy in RIR intervention and therapeutic approaches for the treatment of ACS.

Exposure to microgravity results in vascular remodeling and cardiovascular dysfunction. To elucidate the mechanism involved in this condition, we investigated whether endoplasmic reticulum (ER) stress during simulated microgravity induced endothelial inflammation and apoptosis in human umbilical vein endothelial cells (HUVECs). Microgravity was simulated by clinorotation in the current study. We examined markers of ER stress, inducible nitric oxide (NO) synthase (iNOS)/NO content, proinflammatory cytokine production, nuclear factor kappa B (NF‐κB)/IκB signaling, NLRP3 inflammasome, and detected apoptosis in HUVECs. We found that the levels of C/EBP homologous protein and glucose‐regulated protein 78, pro‐inflammatory cytokines (IL‐6, TNF‐α, IL‐8, and IL‐1β), and iNOS/NO content were upregulated by clinorotation. ER stress inhibition with tauroursodeoxycholic acid or 4‐phenylbutyric acid and iNOS inhibition with 1400 W dramatically suppressed activation of the NF‐κB/IκB pathway and the NLRP3 inflammasome, and decreased the production of pro‐inflammatory cytokines. The increase of apoptosis in HUVECs during clinorotation was significantly suppressed by inhibiting ER stress, iNOS activity, NF‐κB/IκB, and the NLRP3 inflammasome signaling pathway. Therefore, simulated microgravity causes ER stress in HUVECs, and subsequently activates iNOS/NO‐NF‐κB/IκB and the NLRP3 inflammasome signaling pathway, which have key roles in the induction of endothelial inflammation and apoptosis.

Exposure to microgravity results in cardiovascular deconditioning, and cerebrovascular oxidative stress injury has been suggested to occur. To elucidate the mechanism for this condition, we investigated whether simulated microgravity induces mitochondrial dysfunction in rat arteries. Four‐week hindlimb unweighting (HU) was used to simulate microgravity in rats. Mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential (Δψm), mitochondrial permeability transition pore (mPTP) opening, mitochondrial respiratory control ratio (RCR), MnSOD/GPx activity and expression, and mitochondrial malondialdehyde (MDA) were examined in rat cerebral and mesenteric VSMCs. Compared with the control rats, mitochondrial ROS levels, mPTP opening, and MDA content increased significantly ( P < 0.001, P <0.01, and P <0.01, respectively), Δψm, RCR, MnSOD/GPx activity ( P <0.001 for Δψm and RCR; P <0.05 for MnSOD; and P < 0.001 for GPx activity) and protein abundance of mitochondrial MnSOD/GPx‐1 decreased ( P <0.001 for MnSOD and GPx‐1) in HU rat cerebral but not mesenteric arteries. Chronic treatment with NADPH oxidase inhibitor apocynin and mitochondria‐targeted antioxidant mitoTempol promoted recovery of mitochondrial function in HU rat cerebral arteries, but exerted no effects on HU rat mesenteric arteries. Therefore, simulated microgravity resulted in cerebrovascular mitochondrial dysfunction, and crosstalk between NADPH oxidase and mitochondria participated in the process.—Zhang, R., Ran, H.‐H., Cai, L.‐L, Zhu, L., Sun, J.‐F., Peng, L., Liu, X.‐J., Zhang, L.‐N., Fang, Z., Fan, Y.‐Y., Cui, G. Simulated microgravity induced mitochondrial dysfunction in rat cerebral arteries. FASEB J . 28, 2715–2724 (2014). www.fasebj.org

Purpose: To investigate the prevalence, risk factors of intestinal carbapenem-resistant Enterobacteriaceae (CRE) colonization and bloodstream infection (BSI) caused by CRE in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Methods: We analyzed the clinical data of 185 patients with hematological malignancies who underwent allo-HSCT from May 2019 to December 2021. All patients received regular CRE monitoring by rectal swab during allo-HSCT, and some CRE strains were further identified for carbapenemase phenotypes. The rates, distribution and risk factors of CRE colonization, CRE-induced BSI were analyzed. Results: CRE was detected in 44 of 185 recipients, with colonization rate of 23.8%. A total of 46 strains of CRE were isolated, including 22 Escherichia coli, 17 Klebsiella pneumoniae, three Klebsiella oxytoca, two Enterobacter hormaechei, and two other Enterobacteriaceae. Among the 19 strains identified with carbapenemase phenotypes, eight strains of E. coli produced metal β-lactamase, five K. pneumoniae produced serine carbapenemase, two K. pneumoniae produced metal β-lactamase, two K. oxytoca produced metal β-lactamase, a Citrobacter malonic acid-free produced metal β-lactamase and a Citrobacter freundii produced metal β-lactamase. In 10 patients developed with CRE-related BSI, the types and combined drug sensitivity of strains detected by rectal swab were highly consistent with blood culture. Multivariate analysis revealed that pulmonary infection, perianal infection and carbapenem application in the 3 months pre-transplant were independent risk factors for rectal CRE colonization, while rectal colonization with carbapenem-resistant K. pneumoniae (CR-KP) was an independent risk factor for CRE-induced BSI. The mortality rate within 30 days of CRE-related BSI was 50.0%, and patients receiving multi-drug therapy within 24 hours showed slightly lower mortality than that in the single-drug treatment group. Conclusion: Allo-HSCT patients with CRE-induced BSI have poor prognosis, and CR-KP rectal colonization is an independent risk factor for CRE-related BSI. Rectal swab screening during allo-HSCT could provide early warning for later CRE-induced BSI.