John Elrod | Metabolic Signaling Driving Fibroblast Fate and Cardiac Remodeling.

Описание: Texas Heart Institute Cardiology Grand Rounds on January 27, 2023. Dr. John Elrod. Metabolic Signaling Driving Fibroblast Fate and Cardiac Remodeling.

0:00 Introduction
1:38 Cardiac fibrosis is a feature and contributor to progressive heart failure
3:31 Fibroblast differentiation and fibrosis
7:29 Cardiac Fibrotic Stress Response
8:58 Myofibroblast Differentiation Signaling (circa 2015)
11:55 Molecular mechanisms of mitochondrial calcium exchange
14:15 Mcu MEFs display enhanced myofibroblast formation
19:37 Assessment of chromatin accessibility and gene expression in the myofibroblast
20:18 Myofibroblast gene expression correlates with enhanced chromatin accessibility
21:51 Metabolites Regulate Epigenetic Modifiers
23:39 Stable Isotope Resolved Metabolomics-Carbon Tracing
27:34 Glutaminolysis is required for myofibroblast formation
28:54 Inhibition of glutaminolysis reduces TGFB-mediated global histone demethylation
31:23 Genetic deletion of Gist in activated myofibroblasts protects against cardiac functional decline post-TAC
32:13 Genetic deletion of Gls1 in activated myofibroblasts reduces cardiac fibrosis following pressure-overload
35:29 Evidence for myocardial glutamine production and release in HF
37:52 Inhibition of glutamine synthesis in cardiomyocytes
38:37 Deletion of cardiomyocyte GS hints at Cardiomyocyte-to-fibroblast metabolic crosstalk mediating fibrosis
42:31 Acly deletion in post-activated cardiac fibroblasts
46:09 ACLY-dependent Regions Contain Fibrotic TF Motifs
46:57 ACLY-dependent regulation of the fibroblast gene program (loci specificity)
47:30 Therapeutic targeting of metabolism and epigenetic modifiers to reduce fibrosis