Angiotensin converting enzyme expression in primary pulmonary hypertension.

Schuster, Daniel P.; Crouch, Edmond C.; Parks, William C.; Johnson, Tanya; Botney, Mitchell D.

doi:10.1164/ajrccm.154.4.8887612

Cited by 43 publications

(35 citation statements)

References 6 publications

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“…Our data thus imply that PCEB-ACE activity (as expressed using the enzyme activity parameters in the equation described in Patients and Methods) is preserved. These findings provide the first functional confirmation that the previously described preserved pulmonary capillary ACE expression in IPAH is enzymatically active (13,14).…”

Section: Discussionsupporting

confidence: 85%

“…However, the existence of differences in pulmonary endothelial function between the PAH etiologic types remains a possibility, and we therefore hypothesized that PCEB-ACE activity might differ between common PAH types. Furthermore, preserved pulmonary capillary endothelial ACE immunoreactivity and expression have previously been described in patients with IPAH, but the functional significance of this finding was unknown (13,14). Our data provide evidence that these preserved ACE levels are metabolically active.…”

Section: Pulmonary Arterial Hypertension (Pah) Remainssupporting

confidence: 67%

“…The mechanisms of increased ACE expression in the more proximal vessels in relation to the pathogenesis of PAH remain unknown. Although ACE is thought to contribute to a variety of vascular diseases, including atherosclerosis, renal disease, and, potentially, PAH (1,13,14,16), our data do not allow us to elaborate on its relative effects in the various types of PAH.…”

Section: Discussionmentioning

confidence: 78%

“…Those same previous studies (13,14) also described increased ACE expression in preacinar and intraacinar pulmonary arteries in patients with IPAH as compared with controls, but vessels of more than 20 m in diameter do not appear to present sufficient surface area to contribute significantly to single-pass ACE substrate hydrolysis (16,17). The mechanisms of increased ACE expression in the more proximal vessels in relation to the pathogenesis of PAH remain unknown.…”

Section: Discussionmentioning

confidence: 79%

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Pulmonary capillary endothelial metabolic dysfunction: Severity in pulmonary arterial hypertension related to connective tissue disease versus idiopathic pulmonary arterial hypertension

Langleben¹,

Orfanos²,

Giovinazzo³

et al. 2008

Arthritis & Rheumatism

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Objective. Pulmonary endothelial dysfunction is intertwined with the development and progression of pulmonary arterial hypertension (PAH). Pulmonary endothelium is an active metabolic tissue in healthy human subjects. This study was undertaken to determine the effects of PAH on pulmonary endothelial angiotensin-converting enzyme (ACE) activity and to identify differences between common PAH types, i.e., PAH related to connective tissue disease (PAH-CTD) versus idiopathic PAH (IPAH).Methods. Nineteen patients with PAH-CTD, 25 patients with IPAH, and 23 control subjects were evaluated. The single-pass transpulmonary percent metabolism (%M) and hydrolysis (both reflecting enzyme activity per capillary) of an ACE synthetic substrate were determined. In addition, the calculated functional capillary surface area (FCSA), normalized to body surface area (BSA), was determined.Results. The %M values in patients with PAH-CTD (mean ؎ SEM 53.6 ؎ 3.6%) were significantly reduced compared with those in control subjects (P < 0.01) and those in patients with IPAH (P < 0.03), but were similar between the IPAH and control groups (mean ؎ SEM 66.2 ؎ 3.6% and 74.7 ؎ 2.7%, respectively). Substrate hydrolysis was also significantly reduced in patients with PAH-CTD. The FCSA/BSA was significantly reduced in patients with PAH-CTD (mean ؎ SEM 1,068 ؎ 118 ml/minute/m 2 ) and in patients with IPAH (1,443 ؎ 186 ml/minute/m 2 ) compared with that in controls (2,948 ؎ 245 ml/minute/m 2 ; P < 0.01 for both). At a given cardiac index, the FCSA/BSA tended to be lower in the PAH-CTD group than in the IPAH group. Moreover, unlike in IPAH, a linear relationship between the FCSA/BSA and the diffusing capacity for carbon monoxide (DLCO) was observed in PAH-CTD (r ‫؍‬ 0.54, P < 0.03).Conclusion. The metabolically functional pulmonary capillary bed appears to be reduced to an equal extent in PAH-CTD and IPAH. However, %M and hydrolysis appear to be reduced in PAH-CTD but not in IPAH, reflecting relatively diminished ACE activity on the pulmonary capillary endothelial cells of patients with PAH-CTD, and showing that pulmonary endothelial metabolic function differs between PAH types. This study also provides the first functional evidence that a

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Section: Discussionsupporting

confidence: 85%

Section: Pulmonary Arterial Hypertension (Pah) Remainssupporting

confidence: 67%

Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 79%

See 2 more Smart Citations

Pulmonary capillary endothelial metabolic dysfunction: Severity in pulmonary arterial hypertension related to connective tissue disease versus idiopathic pulmonary arterial hypertension

Langleben¹,

Orfanos²,

Giovinazzo³

et al. 2008

Arthritis & Rheumatism

View full text Add to dashboard Cite

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“…21,22 In previous reports, it was also implied that the D allele of ACE was related to pulmonary hypertension by various causes. 23,24 Furthermore, polymorphism in the 894T allele of eNOS and the D allele of ACE could induce rapid progression of high-altitude pulmonary edema because of hypoxic pulmonary vasoconstriction at a high altitude.…”

Section: Circulation Journal Vol72 January 2008mentioning

confidence: 99%

Implications of Mutations of Activin Receptor-Like Kinase 1 Gene (<i>ALK1</i>) in Addition to Bone Morphogenetic Protein Receptor II Gene (<i>BMPR2</i>) in Children With Pulmonary Arterial Hypertension

Fujiwara

Yagi²,

Matsuoka

et al. 2008

Circ J

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Expression of pulmonary vascular angiotensin-converting enzyme in primary and secondary plexiform pulmonary hypertension

et al. 2000

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The hypothesis for this study was that increased local expression of vascular angiotensin-converting enzyme (ACE) may contribute to the arterial remodelling which accompanies pulmonary hypertension, since angiotensin II (ANG II) is an important mediator of pulmonary vascular cell growth. The expression of ACE was studied by immunohistochemistry in paraffin-embedded lung sections from adults undergoing heart-lung transplantation for severe primary (n=6) and secondary (n=7) pulmonary arterial hypertension (PH), compared with age-matched controls (n=11). An antigen retrieval technique was used prior to incubating sections with the anti-ACE monoclonal antibody, CG2, or the endothelial marker, monoclonal anti-CD31. In control lungs, the highest level of ACE immunostaining was seen in the alveolar capillary endothelium, with less intense staining in small intra-acinar pulmonary arteries and relatively little staining in larger preacinar arteries. ACE immunostaining was virtually absent in lymphatics and veins. In both primary and secondary PH, there was an increase in ACE immunostaining in the endothelium of intra-acinar peripheral pulmonary arteries compared with control lungs, extending to the level of alveolar ducts, as confirmed by semi-quantitative analysis. The increase in endothelial ACE expression in the intra-acinar arteries of patients with primary and secondary PH is consistent with the hypothesis that locally increased production of ANG II may contribute to the process of pulmonary vascular remodelling.

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Angiotensin converting enzyme expression in primary pulmonary hypertension.

Cited by 43 publications

References 6 publications

Pulmonary capillary endothelial metabolic dysfunction: Severity in pulmonary arterial hypertension related to connective tissue disease versus idiopathic pulmonary arterial hypertension

Pulmonary capillary endothelial metabolic dysfunction: Severity in pulmonary arterial hypertension related to connective tissue disease versus idiopathic pulmonary arterial hypertension

Implications of Mutations of Activin Receptor-Like Kinase 1 Gene (<i>ALK1</i>) in Addition to Bone Morphogenetic Protein Receptor II Gene (<i>BMPR2</i>) in Children With Pulmonary Arterial Hypertension

Expression of pulmonary vascular angiotensin-converting enzyme in primary and secondary plexiform pulmonary hypertension

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