Vascular Remodeling in Primary Pulmonary Hypertension: What Role for Transforming Growth Factor-Beta?

Botney, Mitchell D.

doi:10.1055/s-2007-1006365

Cited by 78 publications

(97 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although a limited number of studies have suggested a role for TGF-␤ in hypertensive pulmonary vascular remodeling, 19 its precise role is poorly defined. Immunostaining for TGF-␤ isoforms, especially TGF-␤2 and TGF-␤3, appears to be increased in actively remodeling hypertensive pulmonary arteries in patients with PPH compared with controls.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Primary Pulmonary Hypertension Is Associated With Reduced Pulmonary Vascular Expression of Type II Bone Morphogenetic Protein Receptor

et al. 2002

View full text Add to dashboard Cite

Background-Mutations in the type II receptor for bone morphogenetic protein (BMPR-II), a receptor member of the transforming growth factor-␤ (TGF-␤) superfamily, underlie many familial and sporadic cases of primary pulmonary hypertension (PPH). Methods and Results-Because the sites of expression of BMPR-II in the normal and hypertensive lung are unknown, we studied the cellular localization of BMPR-II and the related type I and II receptors for TGF-␤ by immunohistochemistry in lung sections from patients undergoing heart-lung transplantation for PPH (nϭ11, including 3 familial cases) or secondary pulmonary hypertension (nϭ6) and from unused donor lungs (nϭ4). In situ hybridization was performed for BMPR-II mRNA. Patients were screened for the presence of mutations in BMPR2. In normal lungs, BMPR-II expression was prominent on vascular endothelium, with minimal expression in airway and arterial smooth muscle. In pulmonary hypertension cases, the intensity of BMPR-II immunostaining varied between lesions but involved endothelial and myofibroblast components. Image analysis confirmed that expression of BMPR-II was markedly reduced in the peripheral lung of PPH patients, especially in those harboring heterozygous BMPR2 mutations. A less marked reduction was also observed in patients with secondary pulmonary hypertension. In contrast, there was no difference in level of staining for TGF-␤RII or the endothelial marker CD31. Conclusions-The cellular localization of BMPR-II is consistent with a role in the formation of pulmonary vascular lesions in PPH, and reduced BMPR-II expression may contribute to the process of vascular obliteration in severe pulmonary hypertension.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Immunostaining for TGF-␤ isoforms, especially TGF-␤2 and TGF-␤3, appears to be increased in actively remodeling hypertensive pulmonary arteries in patients with PPH compared with controls. 19 However, TGF-␤ is not a known ligand for BMPR-II, and the cellular localization of BMP expression in the lung is yet to be determined.…”

Section: Discussionmentioning

confidence: 99%

Primary Pulmonary Hypertension Is Associated With Reduced Pulmonary Vascular Expression of Type II Bone Morphogenetic Protein Receptor

et al. 2002

View full text Add to dashboard Cite

show abstract

“…Thereby, the increased extracellular matrix synthesis might be induced by transforming growth factor-␤ subtypes. 30 Apart from the new chances and possibilities opened by array technology, many voices warn against potential pitfalls.…”

Section: Discussionmentioning

confidence: 99%

cDNA Array Hybridization after Laser-Assisted Microdissection from Nonneoplastic Tissue

Fink

Kohlhoff

Stein

et al. 2002

The American Journal of Pathology

View full text Add to dashboard Cite

Differential gene expression can be investigated effectively by cDNA arrays. Because tissue homogenates result inevitably in an average expression of a bulk of different cells, we aimed to combine mRNA profiling with cell-type-specific microdissection. Using a polymerase chain reaction (PCR)-based preamplification technique, the expression profile was shown to be preserved. We modified the existing protocol enabling to apply the total amount of extracted RNA from microdissected cells. A mean amplification factor of nearly 1000 allowed to reduce the demand of initial RNA to ϳ10 ng. This technique was used to investigate intrapulmonary arteries from mouse lungs (ϳ500 cell equivalents). Using filters with 1176 spots, three independent experiments showed a high consistency of expression for the preamplified cDNAs. These profiles differed primarily from those of total lung homogenates. Additionally, in experimental hypoxia-induced pulmonary hypertension, amplified cDNA from intrapulmonary vessels of these lungs was compared to cDNA from vessels dissected from

show abstract

“…TGF-β isoforms 1, -2, and -3 are expressed in hypertensive pulmonary arteries [55], and could signal via activation of smad 2 or 3 by serine phosphorylation, whose expression was documented in pulmonary vascular smooth muscle cells [27]. Recent evidence implicates PDGF in the pathogenesis of both monocrotaline-and chronic hypoxia-induced PH [56].…”

Section: Pathobiologymentioning

confidence: 99%

Pathology of Pulmonary Hypertension

Tuder

Marecki

Richter

et al. 2013

Clinics in Chest Medicine

220

107

View full text Add to dashboard Cite

Vascular Remodeling in Primary Pulmonary Hypertension: What Role for Transforming Growth Factor-Beta?

Cited by 78 publications

References 21 publications

Primary Pulmonary Hypertension Is Associated With Reduced Pulmonary Vascular Expression of Type II Bone Morphogenetic Protein Receptor

Primary Pulmonary Hypertension Is Associated With Reduced Pulmonary Vascular Expression of Type II Bone Morphogenetic Protein Receptor

cDNA Array Hybridization after Laser-Assisted Microdissection from Nonneoplastic Tissue

Pathology of Pulmonary Hypertension

Contact Info

Product

Resources

About