Buysschaert Ian, Schmidt Thomas, Roncal Carmen, Carmeliet Peter, Lambrechts Diether
Vesalius Research Center, K.U.Leuven, Leuven, Belgium.
J Cell Mol Med. 2008 Dec;12(6B):2533-51. doi: 10.1111/j.1582-4934.2008.00515.x.
Angiogenesis is controlled by a balance between pro- and anti-angiogenic factors. Studies in mice and human beings have shown that this balance, as well as the general sensitivity of the endothelium to these factors, is genetically pre-determined. In an effort to dissect this genetic basis, different types of genetic variability have emerged: mutations and translocations in angiogenic factors have been linked to several vascular malformations and haemangiomas, whereas SNPs have been associated with complex genetic disorders, such as cancer, neurodegeneration and diabetes. In addition, copy number alterations of angiogenic factors have been reported in several tumours. More recently, epigenetic changes caused by aberrant DNA methylation or histone acetylation of anti-angiogenic molecules have been shown to determine angiogenesis as well. Initial studies also revealed a crucial role for microRNAs in stimulating or reducing angiogenesis. So far, most of these genetic studies have focused on tumour angiogenesis, but future research is expected to improve our understanding of how genetic variants determine angiogenesis in other diseases. Importantly, these genetic insights might also be of important clinical relevance for the use of anti-angiogenic strategies in cancer or macular degeneration.
血管生成受促血管生成因子和抗血管生成因子之间平衡的控制。对小鼠和人类的研究表明，这种平衡以及内皮细胞对这些因子的总体敏感性是由基因预先决定的。为了剖析这种遗传基础，出现了不同类型的基因变异：血管生成因子中的突变和易位与几种血管畸形和血管瘤有关，而单核苷酸多态性（SNP）与复杂的遗传疾病有关，如癌症、神经退行性变和糖尿病。此外，在几种肿瘤中已报道了血管生成因子的拷贝数改变。最近，抗血管生成分子的异常DNA甲基化或组蛋白乙酰化引起的表观遗传变化也已被证明可决定血管生成。初步研究还揭示了微小RNA在刺激或减少血管生成中的关键作用。到目前为止，这些遗传研究大多集中在肿瘤血管生成上，但未来的研究有望增进我们对基因变异如何决定其他疾病中血管生成的理解。重要的是，这些遗传学见解对于在癌症或黄斑变性中使用抗血管生成策略可能也具有重要的临床意义。
