Fast relaxation and desensitization of angiotensin II contraction in the pulmonary artery via AT1R and Akt-mediated phosphorylation of muscular eNOS

Kim, Hae Jin; Jang, Jung‐Hee; Zhang, Yin Hua; Yoo, Hae Young; Kim, Sung Joon

doi:10.1007/s00424-019-02305-z

Cited by 6 publications

(4 citation statements)

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“…Recent studies have suggested that the VSMCs express eNOS and that VSMC-derived NO can account for vasodilation even in endothelium-denuded conditions ( Han et al, 2013 ). Since the pulmonary circulation is operating with distinctively low arterial pressure, the synergistic effect of EC- and VSMC-derived eNOS might be underlying the characteristic low PA resistances ( Kim et al, 2019 ). Reduced expression of eNOS has been associated with alterations in the structure and endothelial function of the pulmonary vasculature in smokers and children with congenital heart defects ( Barberà et al, 2001 ; Ferreiro et al, 2001 ).…”

Section: Discussionmentioning

confidence: 99%

Reconstruction of the Swine Pulmonary Artery Using a Graft Engineered With Syngeneic Cardiac Pericytes

Alvino

Thomas

Ghorbel

et al. 2021

Front. Bioeng. Biotechnol.

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The neonatal heart represents an attractive source of regenerative cells. Here, we report the results of a randomized, controlled, investigator-blinded preclinical study, which assessed the safety and effectiveness of a matrix graft cellularized with cardiac pericytes (CPs) in a piglet model of pulmonary artery (PA) reconstruction. Within each of five trios formed by 4-week-old female littermate piglets, one element (the donor) was sacrificed to provide a source of CPs, while the other two elements (the graft recipients) were allowed to reach the age of 10 weeks. During this time interval, culture-expanded donor CPs were seeded onto swine small intestinal submucosa (SIS) grafts, which were then shaped into conduits and conditioned in a flow bioreactor. Control unseeded SIS conduits were subjected to the same procedure. Then, recipient piglets were randomized to surgical reconstruction of the left PA (LPA) with unseeded or CP-seeded SIS conduits. Doppler echocardiography and cardiac magnetic resonance imaging (CMRI) were performed at baseline and 4-months post-implantation. Vascular explants were examined using histology and immunohistochemistry. All animals completed the scheduled follow-up. No group difference was observed in baseline imaging data. The final Doppler assessment showed that the LPA’s blood flow velocity was similar in the treatment groups. CMRI revealed a mismatch in the average growth of the grafted LPA and contralateral branch in both treatment groups. Histology of explanted arteries demonstrated that the CP-seeded grafts had a thicker luminal cell layer, more intraparietal arterioles, and a higher expression of endothelial nitric oxide synthase (eNOS) compared with unseeded grafts. Moreover, the LPA stump adjacent to the seeded graft contained more elastin and less collagen than the unseeded control. Syngeneic CP engineering did not accomplish the primary goal of supporting the graft’s growth but was able to improve secondary outcomes, such as the luminal cellularization and intraparietal vascularization of the graft, and elastic remodeling of the recipient artery. The beneficial properties of neonatal CPs may be considered in future bioengineering applications aiming to reproduce the cellular composition of native arteries.

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Section: Discussionmentioning

confidence: 99%

Reconstruction of the Swine Pulmonary Artery Using a Graft Engineered With Syngeneic Cardiac Pericytes

Alvino

Thomas

Ghorbel

et al. 2021

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

show abstract

“…Since the large amount of pulmonary circulation is operating with distinctively low arterial pressure, the relatively prominent role of VSMC eNOS might be underlying the characteristic low resistance of PA resistance. The activation of intrinsic eNOS by the vasoactive agonists may counterbalance the excessive constriction of PA. Experimentally, the compromised contraction could be acutely revealed with the pharmacological inhibition of eNOS as shown in their studies [9,10]. Also, Kim et al demonstrated that the nNOS (NOS1)-and iNOS (NOS2)-specific inhibitors did not affect the contractile response to AngII and thromboxane A2, indicating the specific role of eNOS along with the expression patterns proven by immunohistochemistry [9].…”

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confidence: 97%

“…In this issue of Pflugers Archiv, Kim et al [9] have proposed an intriguing role of the VSMC eNOS in the pulmonary artery (PA). The rat PA showed only a transient contraction to angiotensin II (AngII), which owes to the concomitant activation of the eNOS in PA myocytes that express significantly higher eNOS than the systemic arteries.…”

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confidence: 99%

“…Lastly, but most importantly, it remains elusive whether the significant role of VSMC eNOS is also valid in the human PA. Although Kim et al unequivocally showed eNOS phosphorylation by AngII in the human PA smooth muscle cell-line cells, direct evidence of primary tissue is lacking [9]. Recently, downregulatory changes of VSMC eNOS in systemic hypertension model and histone modification have been reported [11,15].…”

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confidence: 99%

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