Low-intensity pulsed ultrasound therapy suppresses coronary adventitial inflammatory changes and hyperconstricting responses after coronary stent implantation in pigs in vivo.
Low-intensity pulsed ultrasound therapy suppresses coronary adventitial inflammatory changes and hyperconstricting responses after coronary stent implantation in pigs in vivo.
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低强度的脉冲超声治疗抑制了猪体内冠状动脉支架植入后冠状动脉炎症变化和超收缩反应。
DOI：
10.1371/journal.pone.0257175
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Shimokawa H
中科院分区：
文献类型：
--
作者：
Watanabe T;Matsumoto Y;Nishimiya K;Shindo T;Amamizu H;Sugisawa J;Tsuchiya S;Sato K;Morosawa S;Ohyama K;Watanabe-Asaka T;Hayashi M;Kawai Y;Takahashi J;Yasuda S;Shimokawa H
我们证明了冠状动脉外膜炎症在猪体内药物洗脱支架（DES）诱导的冠状动脉过度收缩反应的发病机制中起重要作用。然而，目前还没有治疗冠状动脉外膜炎症的方法。因此，我们开发了低强度脉冲超声（LIPUS）疗法，通过增强血管生成来改善心肌缺血。我们的目的是研究我们的LIPUS治疗是否抑制des诱导的猪体内冠状动脉过度收缩反应，如果是，涉及什么机制。将16只正常雄性猪随机分为左前降支（LAD）冠状动脉植入后的LIPUS组和假治疗组。在LIPUS组中，每隔一天将LIPUS（32个周期，193 mW/cm2）应用于心脏的3个不同水平（支架边缘近端、远端和支架中间段），每个水平20分钟，持续2周。假治疗组治疗方法相同，但不使用LIPUS。在支架植入后4周，我们进行了冠状动脉造影，随后进行了免疫组织学分析。与假手术组相比，LIPUS组对DES边缘LAD中5 -羟色胺的冠状动脉收缩反应明显抑制。此外，LIPUS组体内淋巴转运速度明显快于sham组。DES边缘的组织学分析显示，LIPUS组炎症变化和rho激酶活性明显抑制，与eNOS上调和淋巴血管生成增强有关。这些结果表明，我们的非侵入性LIPUS治疗可用于治疗冠状动脉外膜炎症引起的冠状动脉功能异常，这表明它可能是一种新的、安全的治疗冠状动脉疾病的方法。
We demonstrated that coronary adventitial inflammation plays important roles in the pathogenesis of drug-eluting stent (DES)-induced coronary hyperconstricting responses in pigs in vivo. However, no therapy is yet available to treat coronary adventitial inflammation. We thus developed the low-intensity pulsed ultrasound (LIPUS) therapy that ameliorates myocardial ischemia by enhancing angiogenesis. We aimed to examine whether our LIPUS therapy suppresses DES-induced coronary hyperconstricting responses in pigs in vivo, and if so, what mechanisms are involved. Sixteen normal male pigs were randomly assigned to the LIPUS or the sham therapy groups after DES implantation into the left anterior descending (LAD) coronary artery. In the LIPUS group, LIPUS (32 cycles, 193 mW/cm2) was applied to the heart at 3 different levels (segments proximal and distal to the stent edges and middle of the stent) for 20 min at each level for every other day for 2 weeks. The sham therapy group was treated in the same manner but without LIPUS. At 4 weeks after stent implantation, we performed coronary angiography, followed by immunohistological analysis. Coronary vasoconstricting responses to serotonin in LAD at DES edges were significantly suppressed in the LIPUS group compared with the sham group. Furthermore, lymph transport speed in vivo was significantly faster in the LIPUS group than in the sham group. Histological analysis at DES edges showed that inflammatory changes and Rho-kinase activity were significantly suppressed in the LIPUS group, associated with eNOS up-regulation and enhanced lymph-angiogenesis. These results suggest that our non-invasive LIPUS therapy is useful to treat coronary functional abnormalities caused by coronary adventitial inflammation, indicating its potential for the novel and safe therapeutic approach of coronary artery disease.
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影响因子：
--
作者：
Vilahur G;Padro T;Badimon L
通讯作者：
Badimon L
DOI：
10.1056/nejmoa1809798
发表时间：
2019-02-21
期刊：
The New England journal of medicine
影响因子：
--
作者：
Ridker PM;Everett BM;Pradhan A;MacFadyen JG;Solomon DH;Zaharris E;Mam V;Hasan A;Rosenberg Y;Iturriaga E;Gupta M;Tsigoulis M;Verma S;Clearfield M;Libby P;Goldhaber SZ;Seagle R;Ofori C;Saklayen M;Butman S;Singh N;Le May M;Bertrand O;Johnston J;Paynter NP;Glynn RJ;CIRT Investigators
通讯作者：
CIRT Investigators
影响因子：
3.7
作者：
Hanawa K;Ito K;Aizawa K;Shindo T;Nishimiya K;Hasebe Y;Tuburaya R;Hasegawa H;Yasuda S;Kanai H;Shimokawa H
通讯作者：
Shimokawa H
DOI：
10.1172/jci97192
发表时间：
2018-08-01
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Vieira JM;Norman S;Villa Del Campo C;Cahill TJ;Barnette DN;Gunadasa-Rohling M;Johnson LA;Greaves DR;Carr CA;Jackson DG;Riley PR
通讯作者：
Riley PR
影响因子：
3.3
作者：
Kawana, Akiko;Takahashi, Jun;Shimokawa, Hiroaki
通讯作者：
Shimokawa, Hiroaki