BIOMAT Database Logo BIOMAT Database Logo

CYP26 inhibitor R115866 increases retinoid signaling in intimal smooth muscle cells. 2007

Pauline Ocaya, and Andreas C Gidlöf, and Peder S Olofsson, and Hans Törmä, and Allan Sirsjö
Division of Biomedicine, Department of Clinical Medicine, University of Orebro, 701 82 Orebro, Sweden.

OBJECTIVE Intimal smooth muscle cells (SMCs) are dedifferentiated SMCs that have a powerful ability to proliferate and migrate. This cell-type is responsible for the development of intimal hyperplasia after vascular angioplasty. Retinoids, especially all-trans retinoid acid, are known to regulate many processes activated at sites of vascular injury, including modulation of SMC phenotype and inhibition of SMC proliferation. Intracellular levels of active retinoids are under firm control. A key enzyme is the all-trans retinoic acid-degrading enzyme cytochrome p450 isoform 26 (CYP26). Thus, an alternative approach to exogenous retinoid administration could be to increase the intracellular level of all-trans retinoic acid by blocking CYP26-mediated degradation of retinoids. RESULTS Vascular intimal and medial SMCs expressed CYP26A1 and B1 mRNA. Although medial cells remained unaffected, treatment with the CYP26-inhibitor R115866 significantly increased cellular levels of all-trans retinoic acid in intimal SMCs. The increased levels of all-trans retinoic acid induced retinoid-regulated genes and decreased mitogenesis. CONCLUSIONS Blocking of the CYP26-mediated catabolism mimics the effects of exogenously administrated active retinoids on intimal SMCs. Therefore, CYP26-inhibitors offer a potential new therapeutic approach to vascular proliferative disorders.

UI MeSH Term Description Entries
D008297 Male Males
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D011336 Probability The study of chance processes or the relative frequency characterizing a chance process. Probabilities
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D003577 Cytochrome P-450 Enzyme System A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism. Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D000704 Analysis of Variance A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable. ANOVA,Analysis, Variance,Variance Analysis,Analyses, Variance,Variance Analyses
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001013 Aorta, Thoracic The portion of the descending aorta proceeding from the arch of the aorta and extending to the DIAPHRAGM, eventually connecting to the ABDOMINAL AORTA. Aorta, Ascending,Aorta, Descending,Aortic Arch,Aortic Root,Arch of the Aorta,Descending Aorta,Sinotubular Junction,Ascending Aorta,Thoracic Aorta,Aortic Roots,Arch, Aortic,Ascending Aortas,Junction, Sinotubular,Root, Aortic,Sinotubular Junctions
D012176 Retinoids A group of tetraterpenes, with four terpene units joined head-to-tail. Biologically active members of this class are used clinically in the treatment of severe cystic ACNE; PSORIASIS; and other disorders of keratinization. Retinoid

Related Publications

Pauline Ocaya, and Andreas C Gidlöf, and Peder S Olofsson, and Hans Törmä, and Allan Sirsjö
Topical treatment with CYP26 inhibitor talarozole (R115866) dose dependently alters the expression of retinoid-regulated genes in normal human epidermis.
January 2009, The British journal of dermatology,
Pauline Ocaya, and Andreas C Gidlöf, and Peder S Olofsson, and Hans Törmä, and Allan Sirsjö
Increased retinoid signaling in vascular smooth muscle cells by proinflammatory cytokines.
August 2001, Biochemical and biophysical research communications,
Pauline Ocaya, and Andreas C Gidlöf, and Peder S Olofsson, and Hans Törmä, and Allan Sirsjö
The CYP26 inhibitor R115866 potentiates the effects of all-trans retinoic acid on cultured human epidermal keratinocytes.
March 2009, The British journal of dermatology,
Pauline Ocaya, and Andreas C Gidlöf, and Peder S Olofsson, and Hans Törmä, and Allan Sirsjö
Intimal smooth muscle cells: the context-dependent origin.
November 2010, Circulation,
Pauline Ocaya, and Andreas C Gidlöf, and Peder S Olofsson, and Hans Törmä, and Allan Sirsjö
Vascular smooth muscle cells in intimal hyperplasia, an update.
January 2022, Frontiers in physiology,
Pauline Ocaya, and Andreas C Gidlöf, and Peder S Olofsson, and Hans Törmä, and Allan Sirsjö
Intimal smooth muscle cells and their role in messenchymal activation.
January 1972, Verhandlungen der Deutschen Gesellschaft fur Innere Medizin,
Pauline Ocaya, and Andreas C Gidlöf, and Peder S Olofsson, and Hans Törmä, and Allan Sirsjö
Cultured human uterine smooth muscle cells are retinoid responsive.
May 1997, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.),
Pauline Ocaya, and Andreas C Gidlöf, and Peder S Olofsson, and Hans Törmä, and Allan Sirsjö
M2 signaling in smooth muscle cells.
January 1999, Life sciences,
Pauline Ocaya, and Andreas C Gidlöf, and Peder S Olofsson, and Hans Törmä, and Allan Sirsjö
[Responses of atherosclerotic intimal smooth muscle cells to growth factors].
May 1991, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme,
Pauline Ocaya, and Andreas C Gidlöf, and Peder S Olofsson, and Hans Törmä, and Allan Sirsjö
Regressive and progressive changes of intimal smooth muscle cells in atherosclerosis.
January 1972, Verhandlungen der Deutschen Gesellschaft fur Innere Medizin,
Copied contents to your clipboard!