Renal Denervation Suppresses Coronary Hyperconstricting Responses After Drug-Eluting Stent Implantation in Pigs In Vivo Through the Kidney–Brain–Heart Axis

Uzuka, Hironori; Matsumoto, Yasuharu; Nishimiya, Kensuke; Ohyama, Kazuma; Suzuki, Hideaki; Amamizu, Hirokazu; Morosawa, Shiro; Hirano, Minoru; Shindo, Tomohiko; Kikuchi, Yoku; Hao, Kun; Shiroto, Takashi; Ito, Kenta; Takahashi, Jun; Fukuda, Koji; Miyata, Satoshi; Funaki, Y.; Ishibashi‐Ueda, Hatsue; Yasuda, Satoshi; Shimokawa, Hiroaki

doi:10.1161/atvbaha.117.309777

Cited by 13 publications

(10 citation statements)

References 41 publications

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“…The anti-angiogenic strategy for vasa vasorum may cause intramural hemorrhage as a consequence of increased vascular permeability [ 26 ]. We previously demonstrated that catheter-based renal sympathetic denervation is effective to suppress DES-induced coronary hyperconstricting responses via the kidney-brain-heart-axis in pigs in vivo [ 6 ]. We also developed a balloon-catheter based technique to deliver adenovirus-mediated gene transfer of C-type natriuretic peptide gene in pigs in vivo [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Low-intensity pulsed ultrasound therapy suppresses coronary adventitial inflammatory changes and hyperconstricting responses after coronary stent implantation in pigs in vivo

et al. 2021

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Backgrounds 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. Aims 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. Methods 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. Results 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. Conclusions 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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Section: Discussionmentioning

confidence: 99%

Low-intensity pulsed ultrasound therapy suppresses coronary adventitial inflammatory changes and hyperconstricting responses after coronary stent implantation in pigs in vivo

et al. 2021

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“… 45 – 48 A recent study using pigs discovered that this approach reduced blood pressure and improved cardiovascular functions through its influence on kidney-brain-heart axis with profound changes of plasma renin activity, implicating the involvement of the renal renin-angiotensin system regulation in the process. 49 …”

Section: Reninmentioning

confidence: 99%

Renin-Angiotensin System and Cardiovascular Functions

Mohammadmoradi

Chen

et al. 2018

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123

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“…Catheter-based renal denervation also significantly upregulates the expression of alpha-2 adrenergic receptor-binding sites in the nucleus tractus solitarius, and attenuates adventitial VV enhancement associated with a decrease in SNF. [33]…”

Section: Future Perspectivesmentioning

confidence: 99%

Coronary Artery Spasm and Perivascular Adipose Tissue Inflammation: Insights From Translational Imaging Research

2019

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Perivascular adipose tissue, which constitutes perivascular components along with the adventitial vasa vasorum, plays an important role as a source of various inflammatory mediators in cardiovascular disease. Inflammatory changes in the coronary adventitia are thought to be involved in the pathogenesis of coronary artery spasm and vasospastic angina. Recent advances in translational research using non-invasive imaging modalities, including 18F-fluorodeoxyglucose PET and cardiac CT, have enabled us to visualise perivascular inflammation in the pathogenesis of coronary artery spasm. These modality approaches appear to be clinically useful as a non-invasive tool for examining the presence and severity of vasospastic angina.

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Renal Denervation Suppresses Coronary Hyperconstricting Responses After Drug-Eluting Stent Implantation in Pigs In Vivo Through the Kidney–Brain–Heart Axis

Abstract: These results provide the first evidence that RDN ameliorates drug-eluting stent-induced coronary hyperconstricting responses in pigs in vivo through the kidney-brain-heart axis.

Cited by 13 publications

References 41 publications

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

Renin-Angiotensin System and Cardiovascular Functions

Coronary Artery Spasm and Perivascular Adipose Tissue Inflammation: Insights From Translational Imaging Research

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