Angiotensin receptors in Dupuytren’s disease: a target for pharmacological treatment?

Stephen, Christopher D.; Touil, L.L.; Vaiude, Partha; Singh, Jaipaul; McKirdy, Stuart

doi:10.1080/2000656x.2017.1319846

Cited by 8 publications

(9 citation statements)

References 17 publications

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“…Although beyond the scope of this report, it is exciting to speculate on the possibility of targeting the ESC-like population within DD using RAS modulators, such as ACE inhibitors as previously proposed 43 and inhibitors of cathepsins, such as curcumin 44 for cathepsin B, pepstatin for cathepsin D, 45 and chymostatin 45 for cathepsin G, in the treatment of this condition.…”

Section: Discussionmentioning

confidence: 92%

Expression and Localization of Cathepsins B, D, and G in Dupuytren’s Disease

Tan

Brasch

Schaijik

et al. 2018

Plastic and Reconstructive Surgery - Global Open

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Section: Discussionmentioning

confidence: 92%

Expression and Localization of Cathepsins B, D, and G in Dupuytren’s Disease

Tan

Brasch

Schaijik

et al. 2018

Plastic and Reconstructive Surgery - Global Open

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“…The ESC-like population on the endothelium of the microvessels surrounding cords and nodules of DD expresses components of the RAS: PRR, ACE, AT 1 R, AT 2 R, with ACE and PRR also expressed on the pericytes ( 36 ). Stephen et al ( 49 ) report AT 2 R being more abundant than AT 1 R in DD ( 218 ), which is interesting given the largely unknown role of AT 2 R, which is expressed abundantly in fetal tissue compared to adult tissues. This suggests a potential therapeutic role of AT 2 R antagonists and ACEIs for DD ( 219 ).…”

Section: Embryonic Stem Cell-like Cells the Renin-angiotensin System ...mentioning

confidence: 96%

“…More recently, non-operative treatment with Clostridium histolyticum collagenase injection has been used ( 216 ). The long-term outcomes and complications remain unknown, with repeated use being associated with neuromuscular and coagulation disorders ( 217 , 218 ).…”

Section: Embryonic Stem Cell-like Cells the Renin-angiotensin System ...mentioning

confidence: 99%

Insights Into Vascular Anomalies, Cancer, and Fibroproliferative Conditions: The Role of Stem Cells and the Renin-Angiotensin System

Kilmister

Tan

2022

Front. Surg.

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Cells exhibiting embryonic stem cell (ESC) characteristics have been demonstrated in vascular anomalies (VAs), cancer, and fibroproliferative conditions, which are commonly managed by plastic surgeons and remain largely unsolved. The efficacy of the mTOR inhibitor sirolimus, and targeted therapies that block the Ras/BRAF/MEK/ERK1/2 and PI3KCA/AKT/mTOR pathways in many types of cancer and VAs, further supports the critical role of ESC-like cells in the pathogenesis of these conditions. ESC-like cells in VAs, cancer, and fibroproliferative conditions express components of the renin-angiotensin system (RAS) – a homeostatic endocrine signaling cascade that regulates cells with ESC characteristics. ESC-like cells are influenced by the Ras/BRAF/MEK/ERK1/2 and PI3KCA/AKT/mTOR pathways, which directly regulate cellular proliferation and stemness, and interact with the RAS at multiple points. Gain-of-function mutations affecting these pathways have been identified in many types of cancer and VAs, that have been treated with targeted therapies with some success. In cancer, the RAS promotes tumor progression, treatment resistance, recurrence, and metastasis. The RAS modulates cellular invasion, migration, proliferation, and angiogenesis. It also indirectly regulates ESC-like cells via its direct influence on the tissue microenvironment and by its interaction with the immune system. In vitro studies show that RAS inhibition suppresses the hallmarks of cancer in different experimental models. Numerous epidemiological studies show a reduced incidence of cancer and improved survival outcomes in patients taking RAS inhibitors, although some studies have shown no such effect. The discovery of ESC-like cells that express RAS components in infantile hemangioma (IH) underscores the paradigm shift in the understanding of its programmed biologic behavior and accelerated involution induced by β-blockers and angiotensin-converting enzyme inhibitors. The findings of SOX18 inhibition by R-propranolol suggests the possibility of targeting ESC-like cells in IH without β-adrenergic blockade, and its associated side effects. This article provides an overview of the current knowledge of ESC-like cells and the RAS in VAs, cancer, and fibroproliferative conditions. It also highlights new lines of research and potential novel therapeutic approaches for these unsolved problems in plastic surgery, by targeting the ESC-like cells through manipulation of the RAS, its bypass loops and converging signaling pathways using existing low-cost, commonly available, and safe oral medications.

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“…Dupuytren's disease is another fibrotic disease, for which an overactivation of the local RAS has been described. [66] A recent study dergoing open partial fasciectomy were implanted under the dorsal skin of nude mice. [67] The authors found that a 5-day treatment with C21 significantly inhibited myofibroblast proliferation in the transplanted Dupuytren's disease cord specimens.…”

Section: Dupuytren's Diseasementioning

confidence: 99%

“…Dupuytren's disease is another fibrotic disease, for which an overactivation of the local RAS has been described. [ 66 ] A recent study by Chisholm et al tested treatment with the AT 2 R agonist C21 in a xenograft model of Dupuytren's disease in order to investigate the therapeutic potential of the anti‐fibrotic properties of the AT 2 R. For this purpose, Dupuytren's disease cord specimens from patients undergoing open partial fasciectomy were implanted under the dorsal skin of nude mice. [ 67 ] The authors found that a 5‐day treatment with C21 significantly inhibited myofibroblast proliferation in the transplanted Dupuytren's disease cord specimens.…”

Section: The Cutaneous Renin‐angiotensin System Under Pathophysiologimentioning

confidence: 99%

The role of the renin‐angiotensin system in skin physiology and pathophysiology

Silva

Assersen

Willadsen

et al. 2020

Experimental Dermatology

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From the early days until now, textbook knowledge and research about the renin-angiotensin system (RAS) have focused on the renal, vascular and central effects of the main effector hormone of the system, angiotensin II (Ang II). It is still widely unknown that all the RAS components are also expressed in skin, which is why working on the cutaneous RAS is sometimes like being caught between two stools: the scientific RAS community regards the skin as irrelevant as a target organ for the RAS and the dermatology/skin research community regards the RAS as irrelevant for skin physiology and pathophysiology. Despite this hindrance, the number of publications on the cutaneous RAS has steadily risen since the first description of the expression of all components of the RAS in rodent and human skin and is now in the hundreds. [1,2] These studies have provided strong evidence that the RAS is in fact

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Angiotensin receptors in Dupuytren’s disease: a target for pharmacological treatment?

Abstract: These findings have opened a new avenue for future research involving ACE inhibitors, AT2 agonists, and AT2 antagonists in Dupuytren's disease.

Cited by 8 publications

References 17 publications

Expression and Localization of Cathepsins B, D, and G in Dupuytren’s Disease

Expression and Localization of Cathepsins B, D, and G in Dupuytren’s Disease

Insights Into Vascular Anomalies, Cancer, and Fibroproliferative Conditions: The Role of Stem Cells and the Renin-Angiotensin System

The role of the renin‐angiotensin system in skin physiology and pathophysiology

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