Cardiac Fibrosis Revisited by MicroRNA Therapeutics

Thum, Thomas; Lorenzen, Johan M.

doi:10.1161/circulationaha.112.125013

Cited by 30 publications

(33 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Activated NF- κ B can translocate into the nucleus to promote inflammatory gene expression and collagen synthesis 43, 47) . Phosphorylated JNK can activate activator protein 1, which can migrate to the nucleus to enhance TGF- β and collagen expression in CFs 48) . Here, results showed that IMD 1–53 treatment reversed Hcy-activated NF- κ B and JNK in the ApoE-/- mouse myocardium and in CFs.…”

Section: Discussionmentioning

confidence: 99%

Intermedin<sub>1–53</sub> Protects Against Myocardial Fibrosis by Inhibiting Endoplasmic Reticulum Stress and Inflammation Induced by Homocysteine in Apolipoprotein E-Deficient Mice

Zhang

Hou

et al. 2016

J Atheroscler Thromb

View full text Add to dashboard Cite

Aim: Endoplasmic reticulum stress (ERS) and inflammation participate in cardiac fibrosis. Importantly, a novel paracrine/autocrine peptide intermedin1–53 (IMD1–53) in the heart inhibits myocardial fibrosis in rats. However, the mechanisms are yet to be fully elucidated.Methods: Myocardial fibrosis in apolipoprotein E-deficient (ApoE -/-) mice and neonatal rat cardiac fibroblasts (CFs) were induced using homocysteine (Hcy).Results: IMD1–53 inhibited myocardial fibrosis in vivo and in vitro. Picrosirius red staining showed that IMD1–53 reduced myocardial interstitial collagen deposition in ApoE-/- mice treated with Hcy and decreased the expression of myocardial collagen I and III, which was further verified in rat CFs. IMD1–53 attenuated myocardial hypertrophy, as shown by cardiomyocyte cross-sectional area, ratio of heart weight to body weight, and mRNA levels of atrial natriuretic peptide and brain natriuretic peptide. IMD1–53 inhibited the upregulation of ERS hallmarkers such as glucose-regulated protein 78 (GRP78), GRP94, activating transcription factor 6 (ATF6), ATF4, inositol-requiring enzyme 1α, spliced-X-box-binding protein-1, protein kinase receptor-like ER kinase, and eukaryotic translation initiation factor 2α in mouse myocardium and rat CFs treated with Hcy. In addition, IMD1–53 decreased the production of inflammatory factors such as tumor necrosis factor-α, monocyte chemotactic protein-1, interleukin-6 (IL-6), and IL-1β in the mouse myocardium and rat CFs treated with Hcy. Concurrently, IMD1–53 ameliorated the expression of nuclear factor-κB, transforming growth factor-β1, and c-Jun N-terminal kinase in the mouse myocardium and rat CFs treated with Hcy.Conclusions: IMD potentially protects against myocardial fibrosis induced by Hcy in ApoE-/- mice, possibly via attenuating myocardial ERS and inflammation.

show abstract

Section: Discussionmentioning

confidence: 99%

Intermedin<sub>1–53</sub> Protects Against Myocardial Fibrosis by Inhibiting Endoplasmic Reticulum Stress and Inflammation Induced by Homocysteine in Apolipoprotein E-Deficient Mice

Zhang

Hou

et al. 2016

J Atheroscler Thromb

View full text Add to dashboard Cite

show abstract

“…Data represent average of 2 blinded observers and graphed as mean + standard error of the mean (SEM). *P < .05, **P < .01, ***P < .001. changes in histone acetylation/deacetylation [23][24][25] and differential expression of microRNAs [26][27][28] in the pathogenesis of cardiac disease.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Therapy for the Treatment of Hypertension-Induced Cardiac Hypertrophy and Fibrosis

Watson

Horgan

Neary

et al. 2015

J Cardiovasc Pharmacol Ther

View full text Add to dashboard Cite

show abstract

“…This includes the use of targeted antioxidants or inhibition of the opening of the mitochondrial inner membrane permeability transition pore which is less resistant in these organelles as contrasted to interfibrillar mitochondria [64-66]. Such strategies have included nutriceuticals (flavonoids) [67], pharmaceuticals (cyclosporine A or third-generation β-adrenergic-receptor antagonists) [68], inhaled hydrogen gas [69], or microRNAs [70-72]. …”

Section: Cardioprotective Strategiesmentioning

confidence: 99%

Myofibroblast secretome and its auto-/paracrine signaling

Bomb

Heckle

Sun

et al. 2016

Expert Review of Cardiovascular Therapy

View full text Add to dashboard Cite

Summary Myofibroblasts (myoFb) are phenotypically transformed, contractile fibroblast-like cells expressing α-smooth muscle actin microfilaments. They are integral to collagen fibrillogenesis with scar tissue formation at sites of repair irrespective of the etiologic origins of injury or tissue involved. MyoFb can persist long after healing is complete, where their ongoing turnover of collagen accounts for a progressive structural remodeling of an organ (a.k.a. fibrosis, sclerosis or cirrhosis). Such persistent metabolic activity is derived from a secretome consisting of requisite components in the de novo generation of angiotensin (Ang) II. Autocrine and paracrine signaling induced by tissue AngII is expressed via AT1 receptor ligand binding to respectively promote: i) regulation of myoFb collagen synthesis via the fibrogenic cytokine TGF-β1-Smad pathway; and ii) dedifferentiation and protein degradation of atrophic myocytes immobilized and ensnared by fibrillar collagen at sites of scarring. Several cardioprotective strategies in the prevention of fibrosis and involving myofibroblasts are considered. They include: inducing myoFb apoptosis through inactivation of antiapoptotic proteins; AT1 receptor antagonist to interfere with auto-/paracrine myoFb signaling or to induce counterregulatory expression of ACE2; and attacking the AngII-AT1R-TGF-β1-Smad pathway by antibody or the use of triplex-forming oligonucleotides.

show abstract

Cardiac Fibrosis Revisited by MicroRNA Therapeutics

Cited by 30 publications

References 21 publications

Intermedin<sub>1–53</sub> Protects Against Myocardial Fibrosis by Inhibiting Endoplasmic Reticulum Stress and Inflammation Induced by Homocysteine in Apolipoprotein E-Deficient Mice

Intermedin<sub>1–53</sub> Protects Against Myocardial Fibrosis by Inhibiting Endoplasmic Reticulum Stress and Inflammation Induced by Homocysteine in Apolipoprotein E-Deficient Mice

Epigenetic Therapy for the Treatment of Hypertension-Induced Cardiac Hypertrophy and Fibrosis

Myofibroblast secretome and its auto-/paracrine signaling

Contact Info

Product

Resources

About