Sex-specific eNOS activity and function in human endothelial cells.
Sex-specific eNOS activity and function in human endothelial cells.
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性别特异性的eNOS活性和人类内皮细胞的功能。
DOI：
10.1038/s41598-017-10139-x
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发表时间：
2017-08-29
影响因子：
4.6
通讯作者：
Vicentini LM
中科院分区：
文献类型：
--
作者：
Cattaneo MG;Vanetti C;Decimo I;Di Chio M;Martano G;Garrone G;Bifari F;Vicentini LM
临床和流行病学数据表明，生物性别是心血管疾病（CVD）发生和进展的主要决定因素之一。以内皮型一氧化氮合酶（eNOS）活性失衡为特征的内皮功能受损先于并加速CVD的发展。然而，内皮细胞中eNOS的活性和功能是否存在性别二型性尚不清楚。在这里，通过独立研究人类男性和女性EC，我们发现，女性EC表达更高的eNOS mRNA和蛋白水平在体外和离体。eNOS表达的增加与较高的酶活性和一氧化氮产生有关。eNOS的药理学和遗传学抑制只影响女性EC的迁移特性。在体外血管生成实验证实，发芽主要依赖于eNOS依赖性迁移的女性EC。在方差，从男性内皮细胞的毛细血管生长是独立的eNOS活性，但需要细胞增殖。在这项研究中，我们发现EC的表达，活性和eNOS的功能的性别特异性差异。这种内在的性二态性的内皮细胞应进一步评估，以实现更有效和更精确的策略，用于预防和治疗疾病相关的内皮功能受损，如心血管疾病和病理性血管生成。
Clinical and epidemiological data show that biological sex is one of the major determinants for the development and progression of cardiovascular disease (CVD). Impaired endothelial function, characterized by an imbalance in endothelial Nitric Oxide Synthase (eNOS) activity, precedes and accelerates the development of CVD. However, whether there is any sexual dimorphism in eNOS activity and function in endothelial cells (ECs) is still unknown. Here, by independently studying human male and female ECs, we found that female ECs expressed higher eNOS mRNA and protein levels both in vitro and ex vivo. The increased eNOS expression was associated to higher enzymatic activity and nitric oxide production. Pharmacological and genetic inhibition of eNOS affected migratory properties only in female ECs. In vitro angiogenesis experiments confirmed that sprouting mostly relied on eNOS-dependent migration in female ECs. At variance, capillary outgrowth from male ECs was independent of eNOS activity but required cell proliferation. In this study, we found sex-specific differences in the EC expression, activity, and function of eNOS. This intrinsic sexual dimorphism of ECs should be further evaluated to achieve more effective and precise strategies for the prevention and therapy of diseases associated to an impaired endothelial function such as CVD and pathological angiogenesis.
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影响因子：
7.9
作者：
Addis R;Campesi I;Fois M;Capobianco G;Dessole S;Fenu G;Montella A;Cattaneo MG;Vicentini LM;Franconi F
通讯作者：
Franconi F
DOI：
10.1073/pnas.041359198
发表时间：
2001-02-27
影响因子：
11.1
作者：
Fukumura, D;Gohongi, T;Jain, RK
通讯作者：
Jain, RK
影响因子：
4.8
作者：
Heiss, Maximilian;Hellstrom, Mats;Korff, Thomas
通讯作者：
Korff, Thomas
影响因子：
15.9
作者：
JAFFE, EA;NACHMAN, RL;MINICK, CR
通讯作者：
MINICK, CR
影响因子：
5.4
作者：
Gershoni M;Pietrokovski S
通讯作者：
Pietrokovski S