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侧支动脉研究的未来。

The future of collateral artery research.

作者信息

Hakimzadeh Nazanin, Verberne Hein J, Siebes Maria, Piek Jan J

机构信息

Department of Cardiology, Room B2-250, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.

出版信息

Curr Cardiol Rev. 2014 Feb;10(1):73-86. doi: 10.2174/1573403x113099990001.

Abstract

In the event of obstructive coronary artery disease, collateral arteries have been deemed an alternative blood source to preserve myocardial tissue perfusion and function. Monocytes play an important role in modulating this process, by local secretion of growth factors and extracellular matrix degrading enzymes. Extensive efforts have focused on developing compounds for augmenting the growth of collateral vessels (arteriogenesis). Nonetheless, clinical trials investigating the therapeutic potential of these compounds resulted in disappointing outcomes. Previous studies focused on developing compounds that stimulated collateral vessel growth by enhancing monocyte survival and activity. The limited success of these compounds in clinical studies, led to a paradigm shift in arteriogenesis research. Recent studies have shown genetic heterogeneity between CAD patients with sufficient and insufficient collateral vessels. The genetic predispositions in patients with poorly developed collateral vessels include overexpression of arteriogenesis inhibiting signaling pathways. New directions of arteriogenesis research focus on attempting to block such inhibitory pathways to ultimately promote arteriogenesis. Methods to detect collateral vessel growth are also critical in realizing the therapeutic potential of newly developed compounds. Traditional invasive measurements of intracoronary derived collateral flow index remain the gold standard in quantifying functional capacity of collateral vessels. However, advancements made in hybrid diagnostic imaging modalities will also prove to be advantageous in detecting the effects of pro-arteriogenic compounds.

摘要

在发生阻塞性冠状动脉疾病时,侧支动脉被认为是维持心肌组织灌注和功能的替代血源。单核细胞通过局部分泌生长因子和细胞外基质降解酶,在调节这一过程中发挥重要作用。大量努力集中在开发用于促进侧支血管生长(动脉生成)的化合物上。然而,研究这些化合物治疗潜力的临床试验结果令人失望。以往的研究集中在开发通过增强单核细胞存活和活性来刺激侧支血管生长的化合物。这些化合物在临床研究中的有限成功导致了动脉生成研究的范式转变。最近的研究表明,具有充足和不充足侧支血管的冠心病患者之间存在基因异质性。侧支血管发育不良患者的遗传易感性包括动脉生成抑制信号通路的过度表达。动脉生成研究的新方向集中在试图阻断这种抑制性通路,以最终促进动脉生成。检测侧支血管生长的方法对于实现新开发化合物的治疗潜力也至关重要。传统的侵入性测量冠状动脉衍生的侧支血流指数仍然是量化侧支血管功能能力的金标准。然而,混合诊断成像模式的进展在检测促动脉生成化合物的效果方面也将被证明是有利的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58c0/3968596/f0a827c4f291/CCR-10-73_F1.jpg

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