Tools

LEADER 05152cam a2200673Ii 4500

001 on1268150251;

003 OCoLC;

005 20220726155329.0;

006 m o d ;

007 cr unu||||||||;

008 210914s2021 ncua obm 000 0 eng d;

035 a| (Sirsi) o1268150251;

035 a| (OCoLC)1268150251;

049 a| EREE;

100 1 a| Madipally, Divya Jyothi,e| author.?| UNAUTHORIZED;

245 10 a| Role of epicardial adipose tissue secreted interleukin-34 in fibroblast to myofibroblast transdifferentiation and atrial fibrosis /c| by Divya Jyothi Madipally.;

264 1 a| [Greenville, N.C.] :b| [East Carolina University],c| 2021.;

300 a| 1 online resource (122 pages) :b| color illustrations.;

336 a| textb| txt2| rdacontent;

337 a| computerb| c2| rdamedia;

338 a| online resourceb| cr2| rdacarrier;

347 a| text file;

347 b| PDF;

347 c| 2.073 MB;

490 1 a| ECU Brody School of Medicine dissertation;

538 a| System requirements: Adobe Reader.;

538 a| Mode of access: World Wide Web.;

502 b| Ph. D.c| East Carolina Universityd| 2021;

500 a| Presented to the Faculty of the Department of Pharmacology and Toxicology;

500 a| Advisor: Jacques Robidoux;

500 a| Title from PDF t.p. (viewed July 13, 2022).;

520 3 a| The adiposity of the heart has been proven to be significantly associated with cardiac dysfunction. Chronic low-grade inflammation of the adipose tissue and cardiac fibrosis are common complications in type 2 diabetes mellitus (T2DM). Characterized by excessive deposition of extracellular matrix (ECM) proteins like collagen types I and III, and transdifferentiation of cardiac fibroblasts to myofibroblasts, cardiac fibrosis is majorly involved in the etiology of cardiac remodeling in T2DM. These fibrogenic actions are suggested to be mediated by the inappropriate release of adipocytokines, triggering a local inflammatory state in the heart. The aim of this study was to measure the cytokines secreted by the EAT and evaluate their correlation with atrial fibrosis in patients with T2DM. Sixty-four patients undergoing cardiac surgery were enrolled in this study. Masson's trichrome staining was performed on frozen sections of right atrial appendage (RAA) to quantify myocardial fibrosis. EAT medium was used for measuring 49 cytokines using a combination of multiplex ELISAs. Primary cardiac fibroblasts were incubated with or without Interleukin-34 (IL-34), Transforming Growth Factor-[beta] (TGF-[beta]), and with or without TGF-[beta] receptor (TGF-[beta]R) and CSF1- receptor (CSF1-R) inhibitors. Immunofluorescent staining for [alpha]-Smooth Muscle Actin ([alpha]-SMA) was performed to evaluate fibroblast to myofibroblast transdifferentiation, and western blotting analysis of collagen types-I and III was performed to evaluate fibrogenesis. Histology revealed increased myocardial fibrosis in the RAA of patients with T2DM. Myocardial fibrosis also correlated with the plasma glycated hemoglobin A1c (HbA1c) levels. Of the cytokines secreted by EAT explants 11 correlated with myocardial fibrosis, and 3 correlated with the presence of T2DM. Among these cytokines, IL-34 and soluble IL-6 receptor [beta] were correlating with the RAA fibrosis. Furthermore, IL-34 promoted fibrogenesis in cardiac fibroblasts. Interestingly, neither the inhibition of TGF-[beta]R involved in most fibrotic models nor CSF1-R, the principal receptor for IL-34, attenuated IL-34 induced fibroblast differentiation. In conclusion, elevated levels of IL-34 in the EAT of patients with T2DM correlated with atrial fibrosis and promoted fibroblast to myofibroblast transdifferentiation independent of TGF[beta]-R and CSF1-R.;

504 a| Includes bibliographical references.;

650 2 a| Interleukins.=| ^A926102;

650 2 a| Adipose Tissue.=| ^A921324;

650 2 a| Myofibroblasts.=| ^A1439848;

650 2 a| Cell Transdifferentiation.=| ^A1439845;

650 2 a| Fibrosis.=| ^A939038;

655 2 a| Academic Dissertation.0| (DNLM)D019478?| UNAUTHORIZED;

653 a| Cardiac fibrosis;

653 a| Epicardial adipose tissue;

653 a| Cardiac fibroblasts;

653 a| Type 2 Diabetes Mellitus;

653 a| Interleukin-34;

655 7 a| Academic theses.2| fast0| (OCoLC)fst01726453;

655 7 a| Academic theses.2| lcgft;

655 7 a| Thèses et écrits académiques.2| rvmgf0| (CaQQLa)RVMGF-000001173;

700 1 a| Robidoux, Jacques,e| degree supervisor.=| ^A1169264;

710 2 a| East Carolina University.b| Department of Pharmacology and Toxicology.?| UNAUTHORIZED;

830 0 a| ECU Brody School of Medicine dissertation.?| UNAUTHORIZED;

856 40 u| http://hdl.handle.net/10342/9391z| Access via ScholarShip;

949 o| wjh;

994 a| C0b| ERE;

096 a| QU 107;

596 a| 1 4;

998 a| 5668823;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 5668823-1001l| JNETm| JOYNERr| Ys| Yt| JNE3ETDu| 9/14/2021x| ETDz| JERESOURCE;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 5668823-2001l| HSLELECm| HSLr| Ys| Yt| HEETDu| 9/14/2021x| ETDz| HERESOURCE;

Role of epicardial adipose tissue secreted interleukin-34 in fibroblast to myofibroblast transdifferentiation and atrial fibrosis / by Divya Jyothi Madipally.

Author/creator	Madipally, Divya Jyothi author.
Other author	Robidoux, Jacques, degree supervisor.
Other author	East Carolina University. Department of Pharmacology and Toxicology.
Format	Theses and dissertations
Publication	[Greenville, N.C.] : [East Carolina University], 2021.
Description	1 online resource (122 pages) : color illustrations.
Supplemental Content	Access via ScholarShip
Subjects	Interleukins. Adipose Tissue. Myofibroblasts. Cell Transdifferentiation. Fibrosis.

Series	ECU Brody School of Medicine dissertation ECU Brody School of Medicine dissertation. UNAUTHORIZED
Summary	The adiposity of the heart has been proven to be significantly associated with cardiac dysfunction. Chronic low-grade inflammation of the adipose tissue and cardiac fibrosis are common complications in type 2 diabetes mellitus (T2DM). Characterized by excessive deposition of extracellular matrix (ECM) proteins like collagen types I and III, and transdifferentiation of cardiac fibroblasts to myofibroblasts, cardiac fibrosis is majorly involved in the etiology of cardiac remodeling in T2DM. These fibrogenic actions are suggested to be mediated by the inappropriate release of adipocytokines, triggering a local inflammatory state in the heart. The aim of this study was to measure the cytokines secreted by the EAT and evaluate their correlation with atrial fibrosis in patients with T2DM. Sixty-four patients undergoing cardiac surgery were enrolled in this study. Masson's trichrome staining was performed on frozen sections of right atrial appendage (RAA) to quantify myocardial fibrosis. EAT medium was used for measuring 49 cytokines using a combination of multiplex ELISAs. Primary cardiac fibroblasts were incubated with or without Interleukin-34 (IL-34), Transforming Growth Factor-[beta] (TGF-[beta]), and with or without TGF-[beta] receptor (TGF-[beta]R) and CSF1- receptor (CSF1-R) inhibitors. Immunofluorescent staining for [alpha]-Smooth Muscle Actin ([alpha]-SMA) was performed to evaluate fibroblast to myofibroblast transdifferentiation, and western blotting analysis of collagen types-I and III was performed to evaluate fibrogenesis. Histology revealed increased myocardial fibrosis in the RAA of patients with T2DM. Myocardial fibrosis also correlated with the plasma glycated hemoglobin A1c (HbA1c) levels. Of the cytokines secreted by EAT explants 11 correlated with myocardial fibrosis, and 3 correlated with the presence of T2DM. Among these cytokines, IL-34 and soluble IL-6 receptor [beta] were correlating with the RAA fibrosis. Furthermore, IL-34 promoted fibrogenesis in cardiac fibroblasts. Interestingly, neither the inhibition of TGF-[beta]R involved in most fibrotic models nor CSF1-R, the principal receptor for IL-34, attenuated IL-34 induced fibroblast differentiation. In conclusion, elevated levels of IL-34 in the EAT of patients with T2DM correlated with atrial fibrosis and promoted fibroblast to myofibroblast transdifferentiation independent of TGF[beta]-R and CSF1-R.
General note	Presented to the Faculty of the Department of Pharmacology and Toxicology
General note	Advisor: Jacques Robidoux
General note	Title from PDF t.p. (viewed July 13, 2022).
Dissertation note	Ph. D. East Carolina University 2021
Bibliography note	Includes bibliographical references.
Technical details	System requirements: Adobe Reader.
Technical details	Mode of access: World Wide Web.
Genre/form	Academic theses.
Genre/form	Academic theses.
Genre/form	Thèses et écrits académiques.

Availability

Library	Location	Call Number	Status	Item Actions
	Electronic Resources	Access Content Online	✔ Available

Role of epicardial adipose tissue secreted interleukin-34 in fibroblast to myofibroblast transdifferentiation and atrial fibrosis / by Divya Jyothi Madipally.

Click here for more information about this title

Availability