Role of Extracellular Matrix in Pathophysiology of Patent Ductus Arteriosus: Emphasis on Vascular Remodeling

Lin, Ting‐Yi; Yeh, Jwu‐Lai; Hsu, Jong‐Hau

doi:10.3390/ijms21134761

Cited by 9 publications

(8 citation statements)

References 82 publications

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“…The ductus arteriosus is a shunt between the aorta and the pulmonary artery. After delivery, complete closure usually occurs in most newborns 21 . When the ductus persists, blood that should join the systemic circulation is diverted to the pulmonary circulation due to “ductal steal”.…”

Section: Discussionmentioning

confidence: 99%

Lung ultrasound score in the decision of patent ductus arteriosus closure in neonates

Ozdemir,

Tepe,

Ozlu

et al. 2024

J of Clinical Ultrasound

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PurposeWe aimed to investigate the role of lung ultrasound (LUS) score in the closure of hemodynamically insignificant patent ductus arteriosus (PDA) and the clinical findings of the patients before and after closure.MethodsThe study groups (107 preterm neonates under 34 gestational weeks) were classified as hemodynamically significant PDA (group 1), hemodynamically insignificant PDA with closure therapy (group 2), hemodynamically insignificant PDA without closure therapy (group 3), and no PDA group (group 4) based on the echocardiography. 6‐ and 10‐region LUS scores were compared for each group.ResultsThere was a significant difference between groups 1 and 3 on first, third, and seventh days. In contrast, groups 1 and 2 had similar LUS scores on the first, third, and seventh days. There was a negative correlation between LUS scores on the first and third days and gestational age, birth weight, the first‐ and fifth‐minute APGAR scores, and there was a positive correlation between aortic root to left atrium ratio, and PDA diameter/weight ratio.ConclusionWe observed that LUS scores in patients with hemodynamically insignificant PDA treated with closure therapy were similar to in patients with hemodynamically significant PDA. Thus, LUS score can have role in PDA closure in preterm neonates. However, more comprehensive studies are needed.

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Section: Discussionmentioning

confidence: 99%

Lung ultrasound score in the decision of patent ductus arteriosus closure in neonates

Ozdemir,

Tepe,

Ozlu

et al. 2024

J of Clinical Ultrasound

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“…Mechanisms underlying the regulation of DA patency are complex and not fully understood ( Hung et al, 2018 ; Lin et al, 2020 ). Even though the current clinical management mainly targets the prostaglandin pathway, issues such as adverse effects and incomplete responses have been unsolved ( Hsu et al, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

Cinaciguat Prevents Postnatal Closure of Ductus Arteriosus by Vasodilation and Anti-remodeling in Neonatal Rats

Hung

Liu

et al. 2021

Front. Physiol.

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Closure of the ductus arteriosus (DA) involves vasoconstriction and vascular remodeling. Cinaciguat, a soluble guanylyl cyclase (sGC) activator, was reported with vasodilatory and anti-remodeling effects on pulmonary hypertensive vessels. However, its effects on DA are not understood. Therefore, we investigated whether cinaciguat regulated DA patency and examined its underlying mechanisms. In vivo, we found that cinaciguat (10 mg/kg, i.p. at birth) prevented DA closure at 2 h after birth with luminal patency and attenuated intimal thickening. These anti-remodeling effects were associated with enhanced expression of cyclic guanosine monophosphate (cGMP) in DA. Ex vivo, cinaciguat dilated oxygen-induced DA constriction dose-dependently. Such vasodilatory effect was blunted by KT-5823, a PKG inhibitor. In DA smooth muscle cells (DASMCs), we further showed that cinaciguat inhibited angiotensin II (Ang II)-induced proliferation and migration of DASMCs. In addition, cinaciguat inhibited Ang II-induced mitochondrial reactive oxygen species (ROS) production. Finally, Ang II-activated MAPKs and Akt were also inhibited by cinaciguat. In conclusion, cinaciguat prevents postnatal DA closure by vasodilation and anti-remodeling through the cGMP/PKG pathway. The mechanisms underlying anti-remodeling effects include anti-proliferation and anti-migration, with attenuation of mitochondrial ROS production, MAPKs, and Akt signaling. Thus, this study implicates that sGC activation may be a promising novel strategy to regulate DA patency.

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“…Prostaglandin stimulates SMC migration and hyaluronic acid deposition, amplifying the prostaglandin pathway [ 39 ]. This self-reinforcing pathway is crucial in promoting SMC migration into the subendothelial region [ 40 ]. Nonetheless, molecules independent from such pathways were also identified.…”

Section: Mechanisms Of Anatomical Closurementioning

confidence: 99%

Molecular Mechanisms Underlying Remodeling of Ductus Arteriosus: Looking beyond the Prostaglandin Pathway

Hsu

Lin

Liu

et al. 2021

IJMS

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The ductus arteriosus (DA) is a physiologic vessel crucial for fetal circulation. As a major regulating factor, the prostaglandin pathway has long been the target for DA patency maintenance or closure. However, the adverse effect of prostaglandins and their inhibitors has been a major unsolved clinical problem. Furthermore, a significant portion of patients with patent DA fail to respond to cyclooxygenase inhibitors that target the prostaglandin pathway. These unresponsive medical patients ultimately require surgical intervention and highlight the importance of exploring pathways independent from this well-recognized prostaglandin pathway. The clinical limitations of prostaglandin-targeting therapeutics prompted us to investigate molecules beyond the prostaglandin pathway. Thus, this article introduces molecules independent from the prostaglandin pathway based on their correlating mechanisms contributing to vascular remodeling. These molecules may serve as potential targets for future DA patency clinical management.

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Role of Extracellular Matrix in Pathophysiology of Patent Ductus Arteriosus: Emphasis on Vascular Remodeling

Cited by 9 publications

References 82 publications

Lung ultrasound score in the decision of patent ductus arteriosus closure in neonates

Lung ultrasound score in the decision of patent ductus arteriosus closure in neonates

Cinaciguat Prevents Postnatal Closure of Ductus Arteriosus by Vasodilation and Anti-remodeling in Neonatal Rats

Molecular Mechanisms Underlying Remodeling of Ductus Arteriosus: Looking beyond the Prostaglandin Pathway

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