Targeting Rho-associated coiled-coil forming protein kinase (ROCK) in cardiovascular fibrosis and stiffening

@article{Yu2020TargetingRC,
  title={Targeting Rho-associated coiled-coil forming protein kinase (ROCK) in cardiovascular fibrosis and stiffening},
  author={Brian Yu and Nikola Sladojevi{\'c} and John Blair and James K. Liao},
  journal={Expert Opinion on Therapeutic Targets},
  year={2020},
  volume={24},
  pages={47 - 62}
}
ABSTRACT Introduction: Pathological cardiac fibrosis, through excessive extracellular matrix protein deposition from fibroblasts and pro-fibrotic immune responses and vascular stiffening is associated with most forms of cardiovascular disease. Pathological cardiac fibrosis and stiffening can lead to heart failure and arrythmias and vascular stiffening may lead to hypertension. ROCK, a serine/threonine kinase downstream of the Rho-family of GTPases, may regulate many pro-fibrotic and pro… 
View on Taylor & Francis
europepmc.org
12 Citations
Highly Influential Citations
1
Background Citations
5

12 Citations

Vascular Stiffening Mediated by Rho‐Associated Coiled‐Coil Containing Kinase Isoforms
TLDR
Findings indicate that ROCK1 and ROCK2 mediate both age‐related and pharmacologically induced aortic stiffening, and suggest that inhibition of ROCK2, and to a lesser extent ROCK1, may have therapeutic benefits in preventing age-related vascular stiffening.
Fibrotic Signaling in Cardiac Fibroblasts and Vascular Smooth Muscle Cells: The Dual Roles of Fibrosis in HFpEF and CAD
TLDR
The signaling pathways that are activated in the main extracellular matrix (ECM)-producing cells, namely human cardiac fibroblasts and vascular smooth muscle cells, are reviewed to explore similarities and differences of fibrotic remodeling at these two locations of the heart.
Rho Kinases in Embryonic Development and Stem Cell Research
TLDR
This review presents an overview of the milestone discoveries in ROCK research, and focuses on the current understanding of ROCK signaling in embryonic development, current research status using knockout and knockin mouse models, and stem cell research.
Increased expression of yes-associated protein/YAP and transcriptional coactivator with PDZ-binding motif/TAZ activates intestinal fibroblasts to promote intestinal obstruction in Crohn's disease
TRIM proteins in fibrosis.
  • Hao Qian, Lijuan Chen
  • Biology, Medicine
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
  • 2021
ROCK Inhibition as Potential Target for Treatment of Pulmonary Hypertension
TLDR
Current aspects of ROCK inhibition therapy are discussed in relation to the treatment of PH and RV dysfunction, from cell biology to preclinical and clinical studies.
Insulin-like growth factor-1 directly affects cardiac cellular remodelling via distinct pathways
Reverse Remodeling in Human Heart Failure after Cardiac Resynchronization Therapy Is Associated With Reduced RHO-Kinase Activation
TLDR
In HFrEF patients, 3 months of effective CRT induced reverse myocardial remodeling, and ROCK activation was significantly decreased in circulating leukocytes, which may reflect reverse cardiac remodeling in patients with heart failure.
Role of platelet factor 4 in arteriovenous fistula maturation failure: What do we know so far?
TLDR
An overview of the how PF4-mediated fibrosis determines AVF maturation failure is presented, suggesting that a pro-inflammatory cytokine platelet factor 4 (PF4/CXCL4) is upregulated in veins that fail to mature after AVF creation.
Intracellular Redistribution of Left Ventricular Connexin 43 Contributes to the Remodeling of Electrical Properties of the Heart in Insulin-resistant Elderly Rats
  • D. Billur, Y. Olgar, B. Turan
  • Biology, Medicine
    The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society
  • 2022
TLDR
The data indicate the important role of I-R on long-QT in aging heart through alterations in both Cx43 protein level and localizations, leading to an abnormal spreading of ventricular repolarization in I- R heart.
...
...

References

SHOWING 1-10 OF 164 REFERENCES
Rho-associated coiled-coil-forming kinases (ROCKs): potential targets for the treatment of atherosclerosis and vascular disease.
The Rho Kinases: Critical Mediators of Multiple Profibrotic Processes and Rational Targets for New Therapies for Pulmonary Fibrosis
TLDR
Multiple lines of evidence indicate that ROCK inhibition has great potential to be a powerful therapeutic tool in the treatment of fibrosis, both in the lung and beyond.
The pathogenesis of cardiac fibrosis
TLDR
Both experimental and clinical evidence suggests that cardiac fibrotic alterations may be reversible, and understanding the mechanisms responsible for initiation, progression, and resolution of cardiac fibrosis is crucial to design anti-fibrotic treatment strategies for patients with heart disease.
Fibroblast deletion of ROCK2 attenuates cardiac hypertrophy, fibrosis, and diastolic dysfunction.
TLDR
It is shown that fibroblast ROCK2 is necessary to cause cardiac hypertrophy and fibrosis through the induction CTGF and FGF2, and it is suggested that targeting ROCK2 may have therapeutic benefits in patients with LV diastolic dysfunction.
Myocardin-Related Transcription Factor-A Controls Myofibroblast Activation and Fibrosis in Response to Myocardial Infarction
TLDR
It is concluded that MRTF-A regulates myofibroblast activation and fibrosis in response to the renin–angiotensin system and post-MI remodeling.
Targeted deletion of ROCK1 protects the heart against pressure overload by inhibiting reactive fibrosis
  • Ying-min Zhang, J. Bo, Lei Wei
  • Biology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2006
TLDR
Results indicate that ROCK1 contributes to the development of cardiac fibrosis and induction of fibrogenic cytokines in cardiomyocytes in response to pathological stimuli.
[Cardiac fibrosis].
  • I. Manabe
  • Medicine, Biology
    Nihon rinsho. Japanese journal of clinical medicine
  • 2007
TLDR
The molecular mechanisms involved in the pathogenesis of cardiac fibrosis in various myocardial diseases, including myocardIAL infarction, heart failure with reduced or preserved ejection fraction, genetic cardiomyopathies, and diabetic heart disease are discussed.
Rho-associated kinases are crucial for myofibroblast differentiation and production of extracellular matrix in scleroderma fibroblasts.
TLDR
It is demonstrated that Rock potently stimulates the differentiation of resting fibroblasts into myofibroblast and the production of ECM at biologically relevant concentrations without cell toxicity, indicating that inhibition of Rock might be an interesting novel therapeutic approach for the treatment of SSc.
Rad GTPase inhibits cardiac fibrosis through connective tissue growth factor.
TLDR
The data reveal that Rad deficiency can lead to cardiac fibrosis, and suggests a potential link between decreased Rad levels and increased cardiac Fibrosis in human failing hearts.
Transforming growth factor β and its role in heart disease
TLDR
Therapeutic targeting of TGFβ signaling at ALK1-5 receptor activity level has met with limited success and extensive research is needed to develop therapies based on the components of T GFβ signaling pathway, for instance cardiac dysfunction and heart failure.
...
...