The beneficial effects of angiotensin-converting enzyme II (ACE2) activator in pulmonary hypertension secondary to left ventricular dysfunction

Chen, I-Chen; Lin, Jao-Yu; Liu, Yi-Ching; Chai, Chee‐Yin; Yeh, Jwu‐Lai; Hsu, Jong‐Hau; Wu, Bin–Nan; Dai, Zen‐Kong

doi:10.7150/ijms.48096

Cited by 10 publications

(2 citation statements)

References 38 publications

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“…The renin–angiotensin–aldosterone system (RAAS) has been implicated to play a causative role in PH [ 20 , 21 , 22 , 23 ]. The RAAS affects the occurrence and development of left ventricular hypertrophy of the heart mainly through cell proliferation, cell hypertrophy, and partial myocardial hypertrophy [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Unique Pulmonary Hypertension in Young Children: A Case Series Study

Chen

Liu

et al. 2022

Children

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Pediatric pulmonary hypertension (PH) has a similar clinical presentation to the adult disease but is associated with several additional disorders and challenges that require a specific approach for their fulminant course. With improved care for premature infants, various forms of pulmonary vascular disease have been found in children that did not previously exist. Pediatric PH can begin in utero, resulting in pulmonary vascularity growth abnormalities that may persist into adulthood. Here, we retrospectively reviewed several unique pediatric PH cases from 2000 to 2020 at Kaohsiung Medical University Hospital, Taiwan, a tertiary teaching hospital. Their comorbidities varied and included surfactant dysfunction, bronchopulmonary dysplasia, premature closure of the ductus arteriosus, high levels of renin and aldosterone, and Swyer–James–Macleod syndrome. Their clinical profiles, radiological characteristics, echocardiography, pulmonary angiogram, and therapeutic regimens were recorded. Further, because the underlying causes of pediatric PH were complex and markedly different according to age, adult PH classification may not be applicable to pediatric PH in all settings. We also classified these cases using different systems, including the Panama classification and the Sixth World Symposium on PH, and compared their advantages and disadvantages.

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Section: Discussionmentioning

confidence: 99%

Unique Pulmonary Hypertension in Young Children: A Case Series Study

Chen

Liu

et al. 2022

Children

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“…On the basis of the benefits demonstrated by DIZE in other PH models (18,(21)(22)(23), we aimed to evaluate its effects on a rat model of PAH induced by left pneumonectomy combined with SU5416. We reasoned that in this model there could be an up-regulated expression of ACE, leading to the imbalance between vasoconstriction and vasodilation.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin-Converting Enzyme 2 Activator Ameliorates Severe Pulmonary Hypertension in a Rat Model of Left Pneumonectomy Combined With VEGF Inhibition

et al. 2021

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Background: Pulmonary arterial hypertension (PAH) is a life-threatening and deteriorating disease with no promising therapy available currently due to its diversity and complexity. An imbalance between vasoconstriction and vasodilation has been proposed as the mechanism of PAH. Angiotensin-converting enzyme 2 (ACE2), which catalyzes the hydrolysis of the vasoconstrictor angiotensin (Ang) II into the vasodilator Ang-(1-7), has been shown to be an important regulator of blood pressure and cardiovascular diseases. Herein we hypothesized diminazene aceturate (DIZE), an ACE2 activator, could ameliorate the development of PAH and pulmonary vascular remodeling.Methods: A murine model of PAH was established using left pneumonectomy (PNx) on day 0 followed by injection of a single dose of the VEGF receptor-2 inhibitor SU5416 (25 mg/kg) subcutaneously on day 1. All hemodynamic and biochemical measurements were done at the end of the study on day 42. Animals were divided into 4 groups (n = 6–8/group): (1) sham-operated group, (2) vehicle-treatment group (SuPNx42), (3) early treatment group (SuPNx42/DIZE1−42) with DIZE at 15 mg/kg/day, subcutaneously from day 1 to day 42, and (4) late treatment group (SuPNx42/DIZE29−42) with DIZE from days 29–42.Results: In both the early and late treatment groups, DIZE significantly attenuated the mean pulmonary artery pressure, pulmonary arteriolar remodeling, and right ventricle brain natriuretic peptide (BNP), as well as reversed the overexpression of ACE while up-regulating the expression of Ang-(1-7) when compared with the vehicle-treatment group. In addition, the early treatment group also significantly decreased plasma BNP and increased the expression of eNOS.Conclusions: ACE2 activator has therapeutic potentials for preventing and attenuating the development of PAH in an animal model of left pneumonectomy combined with VEGF inhibition. Activation of ACE2 may thus be a useful therapeutic strategy for the treatment of human PAH.

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Animal models of pulmonary hypertension due to left heart disease

Liu

2022

Anim Models and Exp Med

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Pulmonary hypertension (PH) is a progressive cardiovascular disorder of multiple etiologies that typically ends in death due to right heart failure (HF). Based on the World Health Organization (WHO) classification of PH, it is divided into 5 groups, of which PH due to left heart disease (PH-LHD) is the commonest. PH-LHD is described as a PH subtype with mean pulmonary artery pressure (mPAP) >25 mmHg and pulmonary artery wedge pressure (PAWP) >15 mmHg, 1 although the threshold values of PAWP are controversial. 2 HF caused by LHD is mainly manifested as reduced ejection fraction (HFrEF), with preserved ejection fraction (HFpEF) and leftsided heart valve disease (VHD). 3 The occurrence of PH in patients with LHD is a sign of disease progression. 4 Nevertheless, therapeutic agents directly targeting patients with PH-LHD are not available.Although there have been some studies supporting the treatment of PH-LHD with targeted drugs for PAH, none has been applied to clinical treatment of PH-LHD. [5][6][7][8][9][10][11][12][13][14][15][16] Effective treatments for LHD do not seem to improve PH-LHD, 17 because PH-LHD is divided hemodynamically into pure postcapillary PH and combined pre-and

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The beneficial effects of angiotensin-converting enzyme II (ACE2) activator in pulmonary hypertension secondary to left ventricular dysfunction

Cited by 10 publications

References 38 publications

Unique Pulmonary Hypertension in Young Children: A Case Series Study

Unique Pulmonary Hypertension in Young Children: A Case Series Study

Angiotensin-Converting Enzyme 2 Activator Ameliorates Severe Pulmonary Hypertension in a Rat Model of Left Pneumonectomy Combined With VEGF Inhibition

Animal models of pulmonary hypertension due to left heart disease

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