PTH/PTHrP Receptor Signaling Restricts Arterial Fibrosis in Diabetic LDLR

Animals Aorta / metabolism Atherosclerosis / genetics Cells, Cultured Collagen Type I / genetics Collagen Type I, alpha 1 Chain Collagen Type III / genetics Diabetes Mellitus / genetics Diet, High-Fat Disease Models, Animal Fibrosis Humans Male Mice, Inbred C57BL Mice, Knockout Muscle, Smooth, Vascular / metabolism Myocytes, Smooth Muscle / metabolism Parathyroid Hormone / metabolism Rats Receptor, Parathyroid Hormone, Type 1 / deficiency Receptors, LDL / deficiency Signal Transduction Trans-Activators / genetics Transcription, Genetic Vascular Remodeling
arteriosclerosis cardiovascular diseases collagen fibrosis transcription factors

Journal

Circulation research
ISSN: 1524-4571
Titre abrégé: Circ Res
Pays: United States
ID NLM: 0047103

Informations de publication

Date de publication:
08 05 2020
Historique:
pubmed: 12 3 2020
medline: 25 2 2021
entrez: 12 3 2020
Statut: ppublish

Résumé

The PTH1R (PTH [parathyroid hormone]/PTHrP [PTH-related protein] receptor) is expressed in vascular smooth muscle (VSM) and increased VSM PTH1R signaling mitigates diet-induced arteriosclerosis in LDLR To study the impact of VSM PTH1R deficiency, we generated mice SM22-Cre:PTH1R(fl/fl);LDLR Immunofluorescence and Western blot confirmed PTH1R expression in arterial VSM that was reduced by Cre-mediated knockout. PTH1R-VKO cohorts exhibited increased aortic collagen accumulation in vivo, and VSM cultures from PTH1R-VKO mice elaborated more collagen (2.5-fold; PTH1R signaling restricts collagen production in the VSM lineage, in part, via Mkl-1 regulatory circuits that control collagen gene transcription. Strategies that maintain homeostatic VSM PTH1R signaling, as reflected in extracellular vesicle biomarkers of VSM PTH1R/Mkl-1 action, may help mitigate arteriosclerosis and vascular fibrosis.

Identifiants

DOI: 10.1161/CIRCRESAHA.119.316141 PMID: 32160132 PMC: PMC7524585
pubmed: 32160132
doi: 10.1161/CIRCRESAHA.119.316141
pmc: PMC7524585
mid: NIHMS1576084
doi:

Substances chimiques

COL3A1 protein, mouse 0
Collagen Type I 0
Collagen Type I, alpha 1 Chain 0
Collagen Type III 0
Mrtfa protein, mouse 0
PTH1R protein, mouse 0
Parathyroid Hormone 0
Receptor, Parathyroid Hormone, Type 1 0
Receptors, LDL 0
Trans-Activators 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1363-1378

Subventions

Organisme : NIDDK NIH HHS
ID : P01 DK011794
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL069229
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL114806
Pays : United States

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Auteurs

Abraham Behrmann (A)

From the Internal Medicine, Endocrine Division (A.B., D.Z., L.L., S.-L.C., M.M., B.R., P.S., D.A.T.), UT Southwestern Medical Center, Dallas, TX.

Dalian Zhong (D)

From the Internal Medicine, Endocrine Division (A.B., D.Z., L.L., S.-L.C., M.M., B.R., P.S., D.A.T.), UT Southwestern Medical Center, Dallas, TX.

Li Li (L)

Su-Li Cheng (SL)

From the Internal Medicine, Endocrine Division (A.B., D.Z., L.L., S.-L.C., M.M., B.R., P.S., D.A.T.), UT Southwestern Medical Center, Dallas, TX.

Megan Mead (M)

From the Internal Medicine, Endocrine Division (A.B., D.Z., L.L., S.-L.C., M.M., B.R., P.S., D.A.T.), UT Southwestern Medical Center, Dallas, TX.

Bindu Ramachandran (B)

From the Internal Medicine, Endocrine Division (A.B., D.Z., L.L., S.-L.C., M.M., B.R., P.S., D.A.T.), UT Southwestern Medical Center, Dallas, TX.

Parastoo Sabaeifard (P)

From the Internal Medicine, Endocrine Division (A.B., D.Z., L.L., S.-L.C., M.M., B.R., P.S., D.A.T.), UT Southwestern Medical Center, Dallas, TX.

Mohammad Goodarzi (M)

Biochemistry (M.G., A.L.), UT Southwestern Medical Center, Dallas, TX.

Andrew Lemoff (A)

Biochemistry (M.G., A.L.), UT Southwestern Medical Center, Dallas, TX.

Henry M Kronenberg (HM)

Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston (H.M.K.).

Dwight A Towler (DA)

From the Internal Medicine, Endocrine Division (A.B., D.Z., L.L., S.-L.C., M.M., B.R., P.S., D.A.T.), UT Southwestern Medical Center, Dallas, TX.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › PTH/PTHrP Receptor Signaling Restricts...
questionsmedicales.fr › Système cardiovasculaire › Vaisseaux sanguins › Artères › Aorte › PTH/PTHrP Receptor Signaling Restricts...
questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Artériopathies oblitérantes › Artériosclérose › Athérosclérose › PTH/PTHrP Receptor Signaling Restricts...
questionsmedicales.fr › Cellules › Cellules cultivées › PTH/PTHrP Receptor Signaling Restricts...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Scléroprotéines › Protéines de la matrice extracellulaire › Collagène › Collagènes fibrillaires › Collagène de type I › PTH/PTHrP Receptor Signaling Restricts...
questionsmedicales.fr › Structures macromoléculaires › Chaine alpha-1 du collagène de type I › PTH/PTHrP Receptor Signaling Restricts...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Scléroprotéines › Protéines de la matrice extracellulaire › Collagène › Collagènes fibrillaires › Collagène de type III › PTH/PTHrP Receptor Signaling Restricts...
questionsmedicales.fr › Maladies endocriniennes › Diabète › PTH/PTHrP Receptor Signaling Restricts...
questionsmedicales.fr › Phénomènes physiologiques › Alimentation et nutrition › Phénomènes physiologiques nutritionnels › Régime alimentaire › Alimentation riche en graisse › PTH/PTHrP Receptor Signaling Restricts...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › PTH/PTHrP Receptor Signaling Restricts...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Fibrose › PTH/PTHrP Receptor Signaling Restricts...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › PTH/PTHrP Receptor Signaling Restricts...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › PTH/PTHrP Receptor Signaling Restricts...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › PTH/PTHrP Receptor Signaling Restricts...
questionsmedicales.fr › Tissus › Muscles › Muscles lisses › Muscles lisses vasculaires › PTH/PTHrP Receptor Signaling Restricts...
questionsmedicales.fr › Cellules › Cellules musculaires › Myocytes du muscle lisse › PTH/PTHrP Receptor Signaling Restricts...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Hormones peptidiques › Hormone parathyroïdienne › PTH/PTHrP Receptor Signaling Restricts...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › PTH/PTHrP Receptor Signaling Restricts...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs peptidiques › Récepteurs à l'hormone parathyroïdienne › Récepteur de la parathormone de type 1 › PTH/PTHrP Receptor Signaling Restricts...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs aux lipoprotéines › Récepteurs aux lipoprotéines LDL › PTH/PTHrP Receptor Signaling Restricts...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › PTH/PTHrP Receptor Signaling Restricts...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines virales › Protéines virales régulatrices ou accessoires › Transactivateurs › PTH/PTHrP Receptor Signaling Restricts...
questionsmedicales.fr › Phénomènes génétiques › Expression des gènes › Transcription génétique › PTH/PTHrP Receptor Signaling Restricts...
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiologiques cardiovasculaires › Remodelage vasculaire › PTH/PTHrP Receptor Signaling Restricts...