Genetics, epigenetics and pharmaco-(epi)genomics in angiogenesis.
Genetics, epigenetics and pharmaco-(epi)genomics in angiogenesis.
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DOI：
10.1111/j.1582-4934.2008.00515.x
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发表时间：
2008-12
影响因子：
5.3
通讯作者：
Lambrechts D
中科院分区：
文献类型：
--
作者：
Buysschaert I;Schmidt T;Roncal C;Carmeliet P;Lambrechts D
血管生成受促血管生成因子和抗血管生成因子之间的平衡控制。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素的一般敏感性是由遗传预先决定的。在努力剖析这种遗传基础，不同类型的遗传变异已经出现：血管生成因子的突变和易位与几种血管畸形和血管瘤有关，而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，在几种肿瘤中已经报道了血管生成因子的拷贝数改变。最近，由异常DNA甲基化或抗血管生成分子的组蛋白乙酰化引起的表观遗传变化也被证明可以决定血管生成。最初的研究还揭示了microRNA在刺激或减少血管生成中的关键作用。到目前为止，大多数遗传学研究都集中在肿瘤血管生成上，但未来的研究有望提高我们对遗传变异如何决定其他疾病血管生成的理解。重要的是，这些遗传见解也可能对癌症或黄斑变性中使用抗血管生成策略具有重要的临床相关性。
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.
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