Kardami Elissavet, Detillieux Karen, Ma Xin, Jiang Zhisheng, Santiago Jon-Jon, Jimenez Sarah K, Cattini Peter A
Institute of Cardiovascular Sciences, St. Boniface Research Centre, University of Manitoba, 351 Taché Avenue, Winnipeg, Manitoba, Canada.
Heart Fail Rev. 2007 Dec;12(3-4):267-77. doi: 10.1007/s10741-007-9027-0.
Boosting myocardial resistance to acute as well as chronic ischemic damage would ameliorate the detrimental effects of numerous cardiac pathologies and reduce the probability of transition to heart failure. Experimental cardiology has pointed to ischemic and pharmacological pre- as well as post-conditioning as potent acute cardioprotective manipulations. Additional exciting experimental strategies include the induction of true regenerative and/or angiogenic responses to the damaged heart, resulting in sustained structural and functional beneficial effects. Fibroblast growth factor-2 (FGF-2), an endogenous multifunctional protein with strong affinity for the extracellular matrix and basal lamina and well-documented paracrine, autocrine and intracellular modes of action, has been shown over the years to exert acute and direct pro-survival effects, irrespectively of whether it is administered before, during or after an ischemic insult to the heart. FGF-2 is also a potent angiogenic protein and a crucial agent for the proliferation, expansion, and survival of several cell types including those with stem cell properties. Human clinical trials have pointed to a good safety record for this protein. In this review, we will present a case for the low molecular weight isoform of fibroblast growth factor-2 (lo-FGF-2) as a very promising therapeutic agent to achieve powerful acute as well as sustained benefits for the heart, due to its cytoprotective and regenerative properties.
增强心肌对急性和慢性缺血损伤的抵抗力,将改善多种心脏疾病的有害影响,并降低转变为心力衰竭的可能性。实验心脏病学已指出,缺血预处理和药物预处理以及后处理是有效的急性心脏保护措施。其他令人兴奋的实验策略包括诱导受损心脏产生真正的再生和/或血管生成反应,从而产生持续的结构和功能有益效果。成纤维细胞生长因子-2(FGF-2)是一种内源性多功能蛋白,对细胞外基质和基膜具有很强的亲和力,其旁分泌、自分泌和细胞内作用模式也有充分记录。多年来的研究表明,无论在心脏缺血损伤之前、期间还是之后给药,FGF-2都能发挥急性和直接的促生存作用。FGF-2也是一种强大的血管生成蛋白,是几种细胞类型(包括具有干细胞特性的细胞)增殖、扩张和存活的关键因子。人体临床试验表明这种蛋白具有良好的安全性记录。在本综述中,我们将阐述成纤维细胞生长因子-2的低分子量异构体(lo-FGF-2)作为一种非常有前景的治疗药物的理由,因其具有细胞保护和再生特性,可为心脏带来强大的急性和持续益处。