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Valvular interstitial cells express angiotensinogen and cathepsin D, and generate angiotensin peptides.
Int J Biochem Cell Biol. 1996 Jul; 28(7):807-21.IJ

Abstract

Cells capable of de novo angiotensin (Ang)II generation in the heart remain unidentified. High-density angiotensin converting enzyme (ACE) binding has been localized to sites of high collagen turnover, such as heart valve leaflets and their valvular interstitial cells (VIC). VIC express ACE mRNA and their membrane-bound ACE utilizes AngI as substrate. Whether VIC also express angiotensinogen (Ao) and an aspartyl protease, and whether they generate AngI and II de novo, is presently unknown. We sought to address these questions in serum-deprived cultured VIC. Ao, renin and cathepsin D (Cat-D) mRNA expression was addressed by RT-PCR. Production of Ao, AngI and AngII peptides were measured in VIC-culture media by radioimmunoassay (RIA). Immunoreactive Cat-D was detected by immunofluorescein labeling and Western blotting. Cat-D and renin activities were determined by spectrofluorometric and autoradiographic methods and AngI generation by RIA. Results showed (a) expression of Ao and Cat-D both at mRNA and protein levels; (b) AngI and AngII peptides in culture media; (c) acceleration of AngII production by exogenous AngI (1 nmol/l), which was blocked by lisinopril (0.1 mumol/l); (d) that dexamethasone (0.1 mumol/l) increased AngII production; (e) a 46 kDa immunoreactive Cat-D protein by Western blotting; (f) aspartyl protease activity, using chromogenic and 125I-labeled Ao as substrates, inhibited by pepstatin-A; and (g) the absence of renin mRNA and activity. It is concluded that at both the mRNA and protein levels, cultured VIC express Ao and Cat-D, and can generate AngI and AngII peptides by the action of a non-renin protease Cat-D and ACE, respectively. VIC therefore appear to represent a constitutive nonendothelial cell found in adult rat heart valve leaflets, which are capable of de novo Ang peptide generation.

Authors+Show Affiliations

Division of Cardiology, University of Missouri Health Sciences Center, Columbia 65212, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8925411

Citation

Katwa, L C., et al. "Valvular Interstitial Cells Express Angiotensinogen and Cathepsin D, and Generate Angiotensin Peptides." The International Journal of Biochemistry & Cell Biology, vol. 28, no. 7, 1996, pp. 807-21.
Katwa LC, Tyagi SC, Campbell SE, et al. Valvular interstitial cells express angiotensinogen and cathepsin D, and generate angiotensin peptides. Int J Biochem Cell Biol. 1996;28(7):807-21.
Katwa, L. C., Tyagi, S. C., Campbell, S. E., Lee, S. J., Cicila, G. T., & Weber, K. T. (1996). Valvular interstitial cells express angiotensinogen and cathepsin D, and generate angiotensin peptides. The International Journal of Biochemistry & Cell Biology, 28(7), 807-21.
Katwa LC, et al. Valvular Interstitial Cells Express Angiotensinogen and Cathepsin D, and Generate Angiotensin Peptides. Int J Biochem Cell Biol. 1996;28(7):807-21. PubMed PMID: 8925411.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Valvular interstitial cells express angiotensinogen and cathepsin D, and generate angiotensin peptides. AU - Katwa,L C, AU - Tyagi,S C, AU - Campbell,S E, AU - Lee,S J, AU - Cicila,G T, AU - Weber,K T, PY - 1996/7/1/pubmed PY - 1996/7/1/medline PY - 1996/7/1/entrez SP - 807 EP - 21 JF - The international journal of biochemistry & cell biology JO - Int J Biochem Cell Biol VL - 28 IS - 7 N2 - Cells capable of de novo angiotensin (Ang)II generation in the heart remain unidentified. High-density angiotensin converting enzyme (ACE) binding has been localized to sites of high collagen turnover, such as heart valve leaflets and their valvular interstitial cells (VIC). VIC express ACE mRNA and their membrane-bound ACE utilizes AngI as substrate. Whether VIC also express angiotensinogen (Ao) and an aspartyl protease, and whether they generate AngI and II de novo, is presently unknown. We sought to address these questions in serum-deprived cultured VIC. Ao, renin and cathepsin D (Cat-D) mRNA expression was addressed by RT-PCR. Production of Ao, AngI and AngII peptides were measured in VIC-culture media by radioimmunoassay (RIA). Immunoreactive Cat-D was detected by immunofluorescein labeling and Western blotting. Cat-D and renin activities were determined by spectrofluorometric and autoradiographic methods and AngI generation by RIA. Results showed (a) expression of Ao and Cat-D both at mRNA and protein levels; (b) AngI and AngII peptides in culture media; (c) acceleration of AngII production by exogenous AngI (1 nmol/l), which was blocked by lisinopril (0.1 mumol/l); (d) that dexamethasone (0.1 mumol/l) increased AngII production; (e) a 46 kDa immunoreactive Cat-D protein by Western blotting; (f) aspartyl protease activity, using chromogenic and 125I-labeled Ao as substrates, inhibited by pepstatin-A; and (g) the absence of renin mRNA and activity. It is concluded that at both the mRNA and protein levels, cultured VIC express Ao and Cat-D, and can generate AngI and AngII peptides by the action of a non-renin protease Cat-D and ACE, respectively. VIC therefore appear to represent a constitutive nonendothelial cell found in adult rat heart valve leaflets, which are capable of de novo Ang peptide generation. SN - 1357-2725 UR - https://www.unboundmedicine.com/medline/citation/8925411/Valvular_interstitial_cells_express_angiotensinogen_and_cathepsin_D_and_generate_angiotensin_peptides_ L2 - https://linkinghub.elsevier.com/retrieve/pii/1357-2725(96)00012-X DB - PRIME DP - Unbound Medicine ER -