CD38 deficiency alleviates Ang II-induced vascular remodeling by inhibiting small extracellular vesicle-mediated vascular smooth muscle cell senescence in mice.
CD38 deficiency alleviates Ang II-induced vascular remodeling by inhibiting small extracellular vesicle-mediated vascular smooth muscle cell senescence in mice.
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CD38缺陷通过抑制小鼠小细胞外囊泡介导的血管平滑肌细胞衰老来减轻血管紧张素II诱导的血管重塑
DOI：
10.1038/s41392-021-00625-0
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发表时间：
2021-06-11
影响因子：
39.3
通讯作者：
Xin H
中科院分区：
文献类型：
--
作者：
Gan L;Liu D;Liu J;Chen E;Chen C;Liu L;Hu H;Guan X;Ma W;Zhang Y;He Y;Liu B;Tang S;Jiang W;Xue J;Xin H
CD38是哺乳动物细胞中降解烟酰胺腺嘌呤二核苷酸（NAD）的主要酶。NAD水平下降与代谢综合征和衰老相关疾病密切相关。我们的研究表明，CD38缺乏显著减轻血管紧张素II（Ang II）诱导的小鼠血管重塑，如血压降低;减少血管中膜厚度，中膜-管腔比和胶原沉积;恢复弹性蛋白表达。然而，我们的骨髓移植试验表明，CD38在淋巴细胞中的缺陷导致缺乏对血管紧张素II诱导的血管重塑的保护，这表明CD38对血管紧张素II诱导的血管重塑的影响可能主要依赖于血管平滑肌细胞（VSMCs），而不是淋巴细胞。此外，我们观察到，CD38缺陷或NAD补充剂通过抑制衰老相关的小细胞外囊泡（SA-sEVs）的生物发生、分泌和内化，显著减轻了Ang II诱导的血管衰老，这促进了邻近未受损VSMCs的衰老。此外，我们发现，CD38缺陷对VSMC衰老的保护作用与溶酶体功能障碍的恢复有关，特别是在维持沉默调节蛋白介导的线粒体稳态和激活VSMC中的溶酶体-溶酶体轴方面。总之，我们的研究结果表明，CD38及其相关的细胞内NAD下降是血管紧张素II诱导的VSMC衰老和血管重塑的关键。
CD38 is the main enzyme for nicotinamide adenine dinucleotide (NAD) degradation in mammalian cells. Decreased NAD levels are closely related to metabolic syndromes and aging-related diseases. Our study showed that CD38 deficiency significantly alleviated angiotensin II (Ang II)-induced vascular remodeling in mice, as shown by decreased blood pressures; reduced vascular media thickness, media-to-lumen ratio, and collagen deposition; and restored elastin expression. However, our bone marrow transplantation assay showed that CD38 deficiency in lymphocytes led to lack of protection against Ang II-induced vascular remodeling, suggesting that the effects of CD38 on Ang II-induced vascular remodeling might rely primarily on vascular smooth muscle cells (VSMCs), not lymphocytes. In addition, we observed that CD38 deficiency or NAD supplementation remarkably mitigated Ang II-induced vascular senescence by suppressing the biogenesis, secretion, and internalization of senescence-associated small extracellular vesicles (SA-sEVs), which facilitated the senescence of neighboring non-damaged VSMCs. Furthermore, we found that the protective effects of CD38 deficiency on VSMC senescence were related to restoration of lysosome dysfunction, particularly with respect to the maintenance of sirtuin-mediated mitochondrial homeostasis and activation of the mitochondria–lysosomal axis in VSMCs. In conclusion, our findings demonstrated that CD38 and its associated intracellular NAD decline are critical for Ang II-induced VSMC senescence and vascular remodeling.
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影响因子：
20.8
作者：
Chini CCS;Peclat TR;Warner GM;Kashyap S;Espindola-Netto JM;de Oliveira GC;Gomez LS;Hogan KA;Tarragó MG;Puranik AS;Agorrody G;Thompson KL;Dang K;Clarke S;Childs BG;Kanamori KS;Witte MA;Vidal P;Kirkland AL;De Cecco M;Chellappa K;McReynolds MR;Jankowski C;Tchkonia T;Kirkland JL;Sedivy JM;van Deursen JM;Baker DJ;van Schooten W;Rabinowitz JD;Baur JA;Chini EN
通讯作者：
Chini EN
CD38促进血管紧张素II诱导的心脏肥大
影响因子：
5.3
作者：
Guan XH;Hong X;Zhao N;Liu XH;Xiao YF;Chen TT;Deng LB;Wang XL;Wang JB;Ji GJ;Fu M;Deng KY;Xin HB
通讯作者：
Xin HB
影响因子：
37.8
作者：
Kunieda, Takeshige;Minamino, Tohru;Komuro, Issei
通讯作者：
Komuro, Issei
DOI：
10.1016/j.bbrc.2019.03.199
发表时间：
2019-05-28
影响因子：
3.1
作者：
Chini, Claudia;Hogan, Kelly A.;Chini, Eduardo
通讯作者：
Chini, Eduardo
影响因子：
37.8
作者：
Gan, Lu;Xie, Dina;Wang, Yajing
通讯作者：
Wang, Yajing