Expression of angiotensin II type 1 receptor in human cirrhotic livers: Its relation to fibrosis and portal hypertension

Ohsawa, Masahiko; Shirai, Nobuyuki; Sugama, Yoshimi; Fukushima, Hiroko; Suekane, Takehisa; Hirayama, Michihiko; Ehara, Shoichi; Naruko, Takahiko; Ueda, Makiko

doi:10.1016/j.hepres.2005.01.017

Cited by 42 publications

(54 citation statements)

References 41 publications

(74 reference statements)

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“…Of interest, after 2 weeks of fracture healing, the periosteal callus of perindopriltreated animals showed less fibrous tissue compared with controls. Different studies have shown that the RAS contributes to fibrogenesis in a variety of organs like the heart, vascular wall, pancreas, kidney and liver (Kuno et al, 2003;Sun and Weber, 2003;Ikura et al, 2005;Morihara et al, 2006;Shirazi et al, 2007). Accordingly, the reduced fibrous tissue in the periosteal callus area of perindopril-treated animals is compatible with the results of other studies, which have shown reduced fibrous tissue formation after blockade of the RAS (Yoshiji et al, 2007).…”

Section: Discussionsupporting

confidence: 82%

Inhibition of angiotensin‐converting enzyme stimulates fracture healing and periosteal callus formation – role of a local renin‐angiotensin system

Garcia

Schwenzer

Slotta

et al. 2010

British J Pharmacology

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Background and purpose:The renin-angiotensin system (RAS) regulates blood pressure and electrolyte homeostasis. In addition, 'local' tissue-specific RAS have been identified, regulating regeneration, cell growth, apoptosis, inflammation and angiogenesis. Although components of the RAS are expressed in osteoblasts and osteoclasts, a local RAS in bone has not yet been described and there is no information on whether the RAS is involved in fracture healing. Therefore, we studied the expression and function of the key RAS component, angiotensin-converting enzyme (ACE), during fracture healing. Experimental approach: In a murine femur fracture model, animals were treated with the ACE inhibitor perindopril or vehicle only. Fracture healing was analysed after 2, 5 and 10 weeks using X-ray, micro-CT, histomorphometry, immunohistochemistry, Western blotting and biomechanical testing. Key results: ACE was expressed in osteoblasts and hypertrophic chondrocytes in the periosteal callus during fracture healing, accompanied by expression of the angiotensin type-1 and type-2 receptors. Perindopril treatment reduced blood pressure and bone mineral density in unfractured femora. However, it improved periosteal callus formation, bone bridging of the fracture gap and torsional stiffness. ACE inhibition did not affect cell proliferation, but reduced apoptotic cell death. After 10 week treatment, a smaller callus diameter and bone volume after perindopril treatment indicated an advanced stage of bone remodelling. Conclusions: Our study provides evidence for a local RAS in bone that influenced the process of fracture healing. We show for the first time that inhibition of ACE is capable of accelerating bone healing and remodelling.

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Section: Discussionsupporting

confidence: 82%

Inhibition of angiotensin‐converting enzyme stimulates fracture healing and periosteal callus formation – role of a local renin‐angiotensin system

Garcia

Schwenzer

Slotta

et al. 2010

British J Pharmacology

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“…The primary antibodies used are listed in Table 2. Immunohistochemical single staining was performed according to our previous reports [21,22]. Briefly, after quenching endogenous peroxidase activity with 0.3% hydrogen peroxide, frozen sections were incubated with a primary antibody for 1 h at room temperature.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…The extent of LYVE-1-positive or vWf-positive sinusoids was evaluated by the technique reported previously [21,22]. From each immunostained section, four 0.6-mm 2 lobular areas (2.4 mm 2 in total) were randomly chosen and captured by a digital microscope camera.…”

Section: Morphometrymentioning

confidence: 99%

Expression of LYVE-1 in sinusoidal endothelium is reduced in chronically inflamed human livers

et al. 2009

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“…6 In human, AT1-R expression is significantly increased in the fibrous septa of cirrhotic livers. 7 Also, genetic polymorphism in the angiotensinogen gene, which augments those treated with other types of drugs. 19 This result is relevant, since aggressive fibrosis progression in transplanted patients with reinfection of HCV is a serious problem in the field of liver transplantation.…”

mentioning

confidence: 99%

Renin–angiotensin system and progression of chronic liver diseases

Yoshiji

Fukui

2006

J Gastroenterol

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Expression of angiotensin II type 1 receptor in human cirrhotic livers: Its relation to fibrosis and portal hypertension

Cited by 42 publications

References 41 publications

Inhibition of angiotensin‐converting enzyme stimulates fracture healing and periosteal callus formation – role of a local renin‐angiotensin system

Inhibition of angiotensin‐converting enzyme stimulates fracture healing and periosteal callus formation – role of a local renin‐angiotensin system

Expression of LYVE-1 in sinusoidal endothelium is reduced in chronically inflamed human livers

Renin–angiotensin system and progression of chronic liver diseases

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