Functional transformation of macrophage mitochondria in cardiovascular diseases.

Mitochondria are pivotal in the modulation of macrophage activation, differentiation, and survival. Furthermore, macrophages are instrumental in the onset and progression of cardiovascular diseases. Hence, it is imperative to investigate the role of mitochondria within macrophages in the context of cardiovascular disease. In this review, we provide an updated description of the origin and classification of cardiac macrophages and also focused on the relationship between macrophages and mitochondria in cardiovascular diseases with respect to (1) proinflammatory or anti-inflammatory macrophages, (2) macrophage apoptosis, (3) macrophage pyroptosis, and (4) macrophage efferocytosis. Clarifying the relationship between mitochondria and macrophages can aid the exploration of novel therapeutic strategies for cardiovascular disease.

CXCL4:NLRP3-mediated pyroptosis product that regulates cardiac fibrosis.

Severe myocarditis is often accompanied by cardiac fibrosis, but the underlying mechanism has not been fully elucidated. NOD-like receptor protein 3 (NLRP3) inflammation is involved in the development of myocarditis and is closely related to the form of cell death. Inhibiting pyroptosis mediated by NLRP3 inflammasome can reduce cardiac fibrosis, although its exact mechanism remains unknown. In this study, we induced Viral myocarditis (VMC) via infection of CVB3 to explore the relationship between pyroptosis and fibrosis. Our results showed that intraperitoneal injection of an NLRP3 inhibitor MCC950 or use of NLRP3-/- mice inhibited cardiac pyroptosis mediated by NLRP3 inflammasome in VMC. CXCL4 is a chemokine that has been reported to have pro-inflammatory and pro-fibrotic functions. In VMC, we further found that pyroptosis of Mouse myocardial fibroblasts (MCF) promoted the secretion of CXCL4 by activating Wnt/ß-Catenin signaling. Subsequently, the transcriptome sequencing data showed that CXCL4 could promote cardiac fibrosis by activating PI3K/AKT pathway. In summary, infection of CVB3 induced host oxidative stress to further activate the NLRP3 inflammasome and ultimately lead to heart pyroptosis, in which MCF secreted CXCL4 by activating Wnt/ß-Catenin signaling and CXCL4 participated in cardiac fibrosis by activating PI3K/AKT pathway. Therefore, our findings revealed the role of CXCL4 in VMC and unveiled its underlying mechanism. CXCL4 appears to be a potential target for the treatment of VMC.

CXCL4/CXCR3 axis regulates cardiac fibrosis by activating TGF-ß1/Smad2/3 signaling in mouse viral myocarditis.

BACKGROUND: Severe myocarditis is often accompanied by cardiac fibrosis, but the underlying mechanism has not been fully elucidated. CXCL4 is a chemokine that has been reported to have pro-inflammatory and profibrotic functions. The exact role of CXCL4 in cardiac fibrosis remains unclear. METHODS: Viral myocarditis (VMC) models were induced by intraperitoneal injection of Coxsackie B Type 3 (CVB3). In vivo, CVB3 (100 TCID50) and CVB3-AMG487 (CVB3: 100 TCID50; AMG487: 5 mg/kg) combination were administered in the VMC and VMC+AMG487 groups, respectively. Hematoxylin and eosin staining, severity score, Masson staining, and immunofluorescence staining were performed to measure myocardial morphology in VMC. Enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were performed to quantify inflammatory factors (IL-1ß, IL-6, TNF-α, and CXCL4). Aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatine kinase-myocardial band (CK-MB) levels were analyzed by commercial kits. CXCL4, CXCR3B, α-SMA, TGF-ß1, Collagen I, and Collagen III were determined by Western blot and immunofluorescence staining. RESULTS: In vivo, CVB3-AMG487 reduced cardiac injury, α-SMA, Collagen I and Collagen III levels, and collagen deposition in VMC+AMG487 group. Additionally, compared with VMC group, VMC+AMG group decreased the levels of inflammatory factors (IL-1ß, IL-6, and TNF-α). In vitro, CXCL4/CXCR3B axis activation TGF-ß1/Smad2/3 pathway promote mice cardiac fibroblasts differentiation. CONCLUSION: CXCL4 acts as a profibrotic factor in TGF-ß1/Smad2/3 pathway-induced cardiac fibroblast activation and ECM synthesis, and eventually progresses to cardiac fibrosis. Therefore, our findings revealed the role of CXCL4 in VMC and unveiled its underlying mechanism. CXCL4 appears to be a potential target for the treatment of VMC.

Double-center randomized controlled trial on post-stroke shoulder pain treated by electroacupuncture combined with Tuina / 中国针灸

<p><b>OBJECTIVE</b>To evaluate clinical therapeutic effect of post-stroke shoulder pain treated by acupuncture combined with Tuina.</p><p><b>METHODS</b>Three hundred cases of post-stroke shoulder pain were randomly divided into an acupuncture and Tuina group and a rehabilitation group by double-center randomized controlled clinical trial method. In acupuncture and Tuina group, normalized electroacupuncture and Tuina therapy were applied, that was electroacupuncture at main points, such as Chize (LU 5), Quze (PC 3), Shaohai (HT 3), Jianyu (LI 15), Jianliao (TE 14) and Jianjing (GB 21),etc., combined with traditional Tuina manipulations; in rehabilitation group, the rehabilitation methods such as the electrostimulation through nervus cutaneus and the squeezing and stabilizing manipulations of Proprioceptive Neuromuscular Facilitation (PNF), etc. were applied. The treatment courses of both groups were 6 weeks. The main therapeutic effect indices were the Assessment Face Scale (AFS) for pain when shoulder was in passive motion and the Fugl-Meyer Motor Assessment for upper limbs active function; the secondary indices were the moditied Rankin Scale (mRS) and the clinical incidences of shoulder-hand syndrome of hemiplegia and shoulder joint subluxation of hemiplegia.</p><p><b>RESULTS</b>After 6 weeks treatment and 12 weeks follow-up, AFS score, Fugl-Meyer motor assessment of upper limbs active function and mRS evaluation in acupuncture and Tuina group were more obviously improved than those in rehabilitation group (P < 0.05, P < 0.01). Although the clinical incidences of shoulder-hand syndrome of hemiplegia and shoulder joint subluxation of hemiplegia in acupuncture and Tuina group was equal to those in rehabilitation group [3.55% (5/141) vs 8.45% (12/142), 1.42% (2/141) vs 5.63% (8/142), both P > 0.05], the data indicated that there was a superiority tendency in acupuncture and Tuina group.</p><p><b>CONCLUSION</b>The combined therapy of electroacupuncture and Tuina is a normative manipulation, and the therapeutic effect is satisfying for post-stroke shoulder pain, superior to that of comprehensive rehabilitation treatment.</p>