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免疫学中的性别差异：暴露于血管内皮生长因子受体阻断剂的雄性大鼠实验性肺动脉高压的发展更为严重。

Sex Differences in Immunology: More Severe Development of Experimental Pulmonary Hypertension in Male Rats Exposed to Vascular Endothelial Growth Factor Receptor Blockade.

作者信息

Guihaire Julien, Deuse Tobias, Wang Dong, Fadel Elie, Reichenspurner Hermann, Schrepfer Sonja

机构信息

TSI Laboratory, University Heart Center Hamburg, 20246 Hamburg, Germany.

TSI Laboratory, University Heart Center Hamburg, 20246 Hamburg, Germany ; Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, 20246 Hamburg, Germany ; Cardiovascular Surgery, University Heart Center Hamburg, 20246 Hamburg, Germany.

出版信息

Biomed Res Int. 2015;2015:765292. doi: 10.1155/2015/765292. Epub 2015 Sep 1.

DOI:10.1155/2015/765292
PMID:26421302
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4569774/
Abstract

BACKGROUND

The epidemiology of pulmonary hypertension (PH) is characterized by a female preponderance, whereas males share higher severity of the disease.

OBJECTIVE

To compare the severity of experimental PH between male and female athymic rats.

METHODS

PH was induced in 11 male and 11 female athymic rats (resp., SU_M and SU_F groups) using an inhibitor of VEGF-receptors I and II, semaxanib (40 mg/kg). After 28 days, right ventricular (RV) remodeling, systolic function, and hemodynamics were measured using echocardiography and a pressure-volume admittance catheter. Morphometric analyses of lung vasculature and RV myocardium were performed.

RESULTS

Four weeks after semaxanib injection, RV end-systolic pressure was higher in SU_M than in SU_F. Males developed marked RV enlargement and systolic dysfunction compared to females. Impairment of RV-PA coupling efficiency was observed only in SU_M. The smooth muscle cells of the pulmonary arteries switched from a contractile state to a dedifferentiated state only in males.

CONCLUSIONS

Female athymic rats were protected against the development of severe PH. RV-PA coupling was preserved in females through limitation of pulmonary artery muscularization. Control of smooth muscle cells plasticity may be a promising therapeutic approach to reverse established vascular remodeling in PH patients.

摘要

背景

肺动脉高压（PH）的流行病学特征是女性患病率更高，而男性疾病严重程度更高。

目的

比较雄性和雌性无胸腺大鼠实验性PH的严重程度。

方法

使用血管内皮生长因子受体I和II抑制剂司马沙尼（40mg/kg）诱导11只雄性和11只雌性无胸腺大鼠（分别为SU_M组和SU_F组）发生PH。28天后，使用超声心动图和压力-容积导纳导管测量右心室（RV）重塑、收缩功能和血流动力学。对肺血管系统和RV心肌进行形态计量分析。

结果

司马沙尼注射4周后，SU_M组的RV收缩末期压力高于SU_F组。与雌性相比，雄性出现明显的RV扩大和收缩功能障碍。仅在SU_M组观察到RV-PA耦合效率受损。仅在雄性中，肺动脉平滑肌细胞从收缩状态转变为去分化状态。

结论

雌性无胸腺大鼠对严重PH的发生具有保护作用。通过限制肺动脉肌化，雌性大鼠的RV-PA耦合得以保留。控制平滑肌细胞可塑性可能是逆转PH患者已建立的血管重塑的一种有前景的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ca/4569774/8b0ab9c82f62/BMRI2015-765292.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ca/4569774/eb411f48e532/BMRI2015-765292.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ca/4569774/32d4b636e6cd/BMRI2015-765292.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ca/4569774/145a221c8f86/BMRI2015-765292.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ca/4569774/85d3a0e80a44/BMRI2015-765292.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ca/4569774/8b0ab9c82f62/BMRI2015-765292.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ca/4569774/eb411f48e532/BMRI2015-765292.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ca/4569774/32d4b636e6cd/BMRI2015-765292.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ca/4569774/145a221c8f86/BMRI2015-765292.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ca/4569774/85d3a0e80a44/BMRI2015-765292.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ca/4569774/8b0ab9c82f62/BMRI2015-765292.005.jpg

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