犬心脏二尖瓣退行性疾病研究进展

Research Progress on Mitral Degenerative Diseases of Dogs

黏液瘤样二尖瓣疾病(myxomatous mitral valve disease,MMVD)又称为退行性二尖瓣疾病,是瓣膜发生退行性病变的结果。该病是犬最常见心脏病之一,会导致其发生二尖瓣反流(mitral regurgitation,MR)和左侧充血性心力衰竭(congestive heart failure,CHF)等严重后果。MMVD发病率随年龄增长而增加,在某些品种犬中具有高遗传特性。MMVD的病理变化主要是二尖瓣的增厚、脱垂和腱索的伸长甚至断裂。该病的发病机制尚不完全清晰,目前已有的研究分别从组织细胞层面、遗传学和蛋白质组学及信号通路等方面取得了一定的研究结果。从组织细胞层面研究发现,在犬等物种上证实,MMVD与瓣膜间质细胞(valve interstitial cells,VICs)的活化及细胞外基质(extracellular matrix,ECM)中胶原和蛋白聚糖的沉积相关。从遗传学和蛋白质组学层面研究发现,miRNAs可能参与了MMVD的遗传调控,血液循环中的miRNAs有望成为MMVD患犬CHF的生物标志物。从分子信号通路层面研究发现,MMVD与许多信号通路息息相关,其中研究较多的5-羟色胺(5-hydroxytryptamine,5-HT)和转化生长因子β(transforming growth factor-β,TGF-β)通路在VICs的活化中具有重要作用,同时其还受二尖瓣在心脏收缩和舒张时所受的牵拉和血液冲刷的机械应力影响,两条通路相互影响,促使MMVD的发生和发展。笔者就犬MMVD流行病学特征、病理变化、临床症状、诊断分期、治疗手段和疾病相关机制的研究进展做一综述。

Myxomatous mitral valve disease(MMVD),also known as degenerative mitral valve disease,is the result of valve degeneration.The disease is one of the most common heart diseases in dogs and causes serious consequences such as mitral regurgitation(MR)and left side congestive heart failure(CHF).The incidence of MMVD increases with age and has a high genetic characteristic in certain breeds of dogs.The pathological changes of MMVD are mainly mitral valve thickening,prolapse and elongation or rupture of the tendinous cord.The pathogenesis of the disease is still not completely clear,and the existing studies have obtained certain results from the aspects of tissue cell level,genetics and proteomics,and signaling pathways.Studies at the tissue and cell level have shown that MMVD is associated with the activation of valve interstitial cell(VIC)and the deposition of collagen and proteoglycan in the extracellular matrix(ECM)in dogs and other species.Genetic and proteomic studies have shown that miRNAs may be involved in the genetic regulation of MMVD,and blood circulating miRNAs are expected to be biomarkers of CHF in dogs with MMVD.From the molecular signaling pathway level,MMVD is closely related to many signaling pathways.Among them,the well-studied 5-hydroxytryptamine(5-HT)and transforming growth factor-β(TGF-β)pathways play important roles in the activation of VICs.At the same time,the mitral valve is also affected by the mechanical stress of pulling and blood flushing during the contraction and relaxation of the heart,and the two pathways interact with each other to promote the occurrence and development of MMVD.In this review,the epidemiological characteristics,pathological changes,clinical symptoms,diagnostic stages,therapeutic methods and disease-related mechanisms of MMVD in dogs were reviewed.