Retinoblastoma protein: A molecular regulator of chronic venous insufficiency

Peter J. Pappas, Gary A. Gwertzman, David O. Defouw, Frank T. Padberg, Michael Silva, Walter N. Durán, Robert W. Hobson

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Purpose. Chronic venous insufficiency (CVI) and varicose vein (VV) formation is characterized histologically by the transformation of smooth muscle cells (SMC) from a contractile to a secretory phenotype and by intense collagen deposition. The subcellular regulation point for these processes may be the retinoblastoma protein (pRb), a known inhibitor of cellular proliferation and regulator of differentiation. We hypothesize that pRb phosphorylation is associated with VV formation and functions as a possible subcellular regulator. Methods. Patients were separated into two groups. Group 1 (n = 6) consisted of vein specimens obtained from patients undergoing coronary artery bypass grafting. Group 2 (n = 6) consisted of patients with symptomatic CVI and duplex confirmed refluxing greater saphenous veins (GSVs) who required GSV stripping. Western blots of GSV protein extracts were performed with anti-human pRb monoclonal antibodies and the degree of nonphosphorylated and phosphorylated pRb was determined. Results were quantified using image analysis of band intensities (computer calibrated intensity units). The ultrastructural appearance of SMCs and the vein wall architecture were qualitatively analyzed with electron microscopy in both groups. Results. Phosphorylated pRb from varicose GSVs exhibited intensities of 523 ± 188 units, while phosphorylated pRb from normal GSVs demonstrated intensities of 153 ± 41 units (P < 0.05). SMCs in varicosed GSVs were surrounded by disorganized collagen deposits and displayed a secretory phenotype with spherical vacuolated cells. SMCs from normal GSVs appeared spindle shaped with a purported contractile phenotype and a well-structured extracellular matrix. Conclusion. Our data demonstrate that VV formation, in patients with CVI, is associated with phosphorylated pRb and the transformation of SMCs from a contractile to a secretory ultrastructural morphology. The data suggest that SMC dedifferentiation is regulated by pRb and that disinhibition of this protein (phosphorylation) may be an significant factor in the development of lower extremity varicosities.

Original languageEnglish (US)
Pages (from-to)149-153
Number of pages5
JournalJournal of Surgical Research
Volume76
Issue number2
DOIs
StatePublished - May 1998
Externally publishedYes

Fingerprint

Retinoblastoma Protein
Venous Insufficiency
Saphenous Vein
Staphylococcal Protein A
Varicose Veins
Phenotype
Smooth Muscle Myocytes
Veins
Collagen
Cell Dedifferentiation
Phosphorylation
Coronary Artery Bypass
Extracellular Matrix
Lower Extremity
Electron Microscopy
Proteins
Western Blotting
Monoclonal Antibodies
Cell Proliferation

Keywords

  • Chronic venous insufficiency
  • Retinoblastoma protein

ASJC Scopus subject areas

  • Surgery

Cite this

Pappas, P. J., Gwertzman, G. A., Defouw, D. O., Padberg, F. T., Silva, M., Durán, W. N., & Hobson, R. W. (1998). Retinoblastoma protein: A molecular regulator of chronic venous insufficiency. Journal of Surgical Research, 76(2), 149-153. https://doi.org/10.1006/jsre.1998.5310

Retinoblastoma protein : A molecular regulator of chronic venous insufficiency. / Pappas, Peter J.; Gwertzman, Gary A.; Defouw, David O.; Padberg, Frank T.; Silva, Michael; Durán, Walter N.; Hobson, Robert W.

In: Journal of Surgical Research, Vol. 76, No. 2, 05.1998, p. 149-153.

Research output: Contribution to journalArticle

Pappas, PJ, Gwertzman, GA, Defouw, DO, Padberg, FT, Silva, M, Durán, WN & Hobson, RW 1998, 'Retinoblastoma protein: A molecular regulator of chronic venous insufficiency', Journal of Surgical Research, vol. 76, no. 2, pp. 149-153. https://doi.org/10.1006/jsre.1998.5310
Pappas, Peter J. ; Gwertzman, Gary A. ; Defouw, David O. ; Padberg, Frank T. ; Silva, Michael ; Durán, Walter N. ; Hobson, Robert W. / Retinoblastoma protein : A molecular regulator of chronic venous insufficiency. In: Journal of Surgical Research. 1998 ; Vol. 76, No. 2. pp. 149-153.
@article{48e1ea1fe4b94e308a70b9b633368a78,
title = "Retinoblastoma protein: A molecular regulator of chronic venous insufficiency",
abstract = "Purpose. Chronic venous insufficiency (CVI) and varicose vein (VV) formation is characterized histologically by the transformation of smooth muscle cells (SMC) from a contractile to a secretory phenotype and by intense collagen deposition. The subcellular regulation point for these processes may be the retinoblastoma protein (pRb), a known inhibitor of cellular proliferation and regulator of differentiation. We hypothesize that pRb phosphorylation is associated with VV formation and functions as a possible subcellular regulator. Methods. Patients were separated into two groups. Group 1 (n = 6) consisted of vein specimens obtained from patients undergoing coronary artery bypass grafting. Group 2 (n = 6) consisted of patients with symptomatic CVI and duplex confirmed refluxing greater saphenous veins (GSVs) who required GSV stripping. Western blots of GSV protein extracts were performed with anti-human pRb monoclonal antibodies and the degree of nonphosphorylated and phosphorylated pRb was determined. Results were quantified using image analysis of band intensities (computer calibrated intensity units). The ultrastructural appearance of SMCs and the vein wall architecture were qualitatively analyzed with electron microscopy in both groups. Results. Phosphorylated pRb from varicose GSVs exhibited intensities of 523 ± 188 units, while phosphorylated pRb from normal GSVs demonstrated intensities of 153 ± 41 units (P < 0.05). SMCs in varicosed GSVs were surrounded by disorganized collagen deposits and displayed a secretory phenotype with spherical vacuolated cells. SMCs from normal GSVs appeared spindle shaped with a purported contractile phenotype and a well-structured extracellular matrix. Conclusion. Our data demonstrate that VV formation, in patients with CVI, is associated with phosphorylated pRb and the transformation of SMCs from a contractile to a secretory ultrastructural morphology. The data suggest that SMC dedifferentiation is regulated by pRb and that disinhibition of this protein (phosphorylation) may be an significant factor in the development of lower extremity varicosities.",
keywords = "Chronic venous insufficiency, Retinoblastoma protein",
author = "Pappas, {Peter J.} and Gwertzman, {Gary A.} and Defouw, {David O.} and Padberg, {Frank T.} and Michael Silva and Dur{\'a}n, {Walter N.} and Hobson, {Robert W.}",
year = "1998",
month = "5",
doi = "10.1006/jsre.1998.5310",
language = "English (US)",
volume = "76",
pages = "149--153",
journal = "Journal of Surgical Research",
issn = "0022-4804",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Retinoblastoma protein

T2 - A molecular regulator of chronic venous insufficiency

AU - Pappas, Peter J.

AU - Gwertzman, Gary A.

AU - Defouw, David O.

AU - Padberg, Frank T.

AU - Silva, Michael

AU - Durán, Walter N.

AU - Hobson, Robert W.

PY - 1998/5

Y1 - 1998/5

N2 - Purpose. Chronic venous insufficiency (CVI) and varicose vein (VV) formation is characterized histologically by the transformation of smooth muscle cells (SMC) from a contractile to a secretory phenotype and by intense collagen deposition. The subcellular regulation point for these processes may be the retinoblastoma protein (pRb), a known inhibitor of cellular proliferation and regulator of differentiation. We hypothesize that pRb phosphorylation is associated with VV formation and functions as a possible subcellular regulator. Methods. Patients were separated into two groups. Group 1 (n = 6) consisted of vein specimens obtained from patients undergoing coronary artery bypass grafting. Group 2 (n = 6) consisted of patients with symptomatic CVI and duplex confirmed refluxing greater saphenous veins (GSVs) who required GSV stripping. Western blots of GSV protein extracts were performed with anti-human pRb monoclonal antibodies and the degree of nonphosphorylated and phosphorylated pRb was determined. Results were quantified using image analysis of band intensities (computer calibrated intensity units). The ultrastructural appearance of SMCs and the vein wall architecture were qualitatively analyzed with electron microscopy in both groups. Results. Phosphorylated pRb from varicose GSVs exhibited intensities of 523 ± 188 units, while phosphorylated pRb from normal GSVs demonstrated intensities of 153 ± 41 units (P < 0.05). SMCs in varicosed GSVs were surrounded by disorganized collagen deposits and displayed a secretory phenotype with spherical vacuolated cells. SMCs from normal GSVs appeared spindle shaped with a purported contractile phenotype and a well-structured extracellular matrix. Conclusion. Our data demonstrate that VV formation, in patients with CVI, is associated with phosphorylated pRb and the transformation of SMCs from a contractile to a secretory ultrastructural morphology. The data suggest that SMC dedifferentiation is regulated by pRb and that disinhibition of this protein (phosphorylation) may be an significant factor in the development of lower extremity varicosities.

AB - Purpose. Chronic venous insufficiency (CVI) and varicose vein (VV) formation is characterized histologically by the transformation of smooth muscle cells (SMC) from a contractile to a secretory phenotype and by intense collagen deposition. The subcellular regulation point for these processes may be the retinoblastoma protein (pRb), a known inhibitor of cellular proliferation and regulator of differentiation. We hypothesize that pRb phosphorylation is associated with VV formation and functions as a possible subcellular regulator. Methods. Patients were separated into two groups. Group 1 (n = 6) consisted of vein specimens obtained from patients undergoing coronary artery bypass grafting. Group 2 (n = 6) consisted of patients with symptomatic CVI and duplex confirmed refluxing greater saphenous veins (GSVs) who required GSV stripping. Western blots of GSV protein extracts were performed with anti-human pRb monoclonal antibodies and the degree of nonphosphorylated and phosphorylated pRb was determined. Results were quantified using image analysis of band intensities (computer calibrated intensity units). The ultrastructural appearance of SMCs and the vein wall architecture were qualitatively analyzed with electron microscopy in both groups. Results. Phosphorylated pRb from varicose GSVs exhibited intensities of 523 ± 188 units, while phosphorylated pRb from normal GSVs demonstrated intensities of 153 ± 41 units (P < 0.05). SMCs in varicosed GSVs were surrounded by disorganized collagen deposits and displayed a secretory phenotype with spherical vacuolated cells. SMCs from normal GSVs appeared spindle shaped with a purported contractile phenotype and a well-structured extracellular matrix. Conclusion. Our data demonstrate that VV formation, in patients with CVI, is associated with phosphorylated pRb and the transformation of SMCs from a contractile to a secretory ultrastructural morphology. The data suggest that SMC dedifferentiation is regulated by pRb and that disinhibition of this protein (phosphorylation) may be an significant factor in the development of lower extremity varicosities.

KW - Chronic venous insufficiency

KW - Retinoblastoma protein

UR - http://www.scopus.com/inward/record.url?scp=0032079181&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032079181&partnerID=8YFLogxK

U2 - 10.1006/jsre.1998.5310

DO - 10.1006/jsre.1998.5310

M3 - Article

C2 - 9698515

AN - SCOPUS:0032079181

VL - 76

SP - 149

EP - 153

JO - Journal of Surgical Research

JF - Journal of Surgical Research

SN - 0022-4804

IS - 2

ER -