Aging and Transplant Arteriosclerosis in Absence of Alloreactivity and Immunosuppressive Drugs in a Rat Aortic Model: Recipient Age???s Contribution

Calfa, Marian; Aı̈touche, Abdelouahab; Vázquez-Padrón, Roberto I.; Gay-Rabinstein, Carlota; Lasko, David; Badell, John; Farji, Arie; Elhaddad, A.; Liotta, Carlos; Louis, Louis B.; Simmonds, Alric; Pestana, Ivo A.; Pang, Manhui; Li, Sen; Pham, Si M.

doi:10.1097/01.tp.0000163467.93783.c8

Cited by 5 publications

(5 citation statements)

References 34 publications

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“…Interestingly, transplantation of aortic grafts from old rats into young recipients resulted in greater neointima formation [6]. Others found young aortas develop thicker neointimas when transplanted into old recipients, whereas the opposite was observed after transplantation of old aortas in young recipients [30]. Our finding that transplantation of PVAT did not mimic the effects of age on neointima formation may be interpreted as pointing to a predominant role of the vessel wall itself, or systemic factors, in response to injury with age.…”

Section: Discussionmentioning

confidence: 55%

Age-Dependent and -Independent Effects of Perivascular Adipose Tissue and Its Paracrine Activities during Neointima Formation

Schütz

Gogiraju

Pavlaki

et al. 2019

IJMS

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Cardiovascular risk factors may act by modulating the composition and function of the adventitia. Here we examine how age affects perivascular adipose tissue (PVAT) and its paracrine activities during neointima formation. Aortic tissue and PVAT or primary aortic smooth muscle cells from male C57BL/6JRj mice aged 52 weeks (“middle-aged”) were compared to tissue or cells from mice aged 16 weeks (“adult”). Vascular injury was induced at the carotid artery using 10% ferric chloride. Carotid arteries from the middle-aged mice exhibited smooth muscle de-differentiation and elevated senescence marker expression, and vascular injury further aggravated media and adventitia thickening. Perivascular transplantation of PVAT had no effect on these parameters, but age-independently reduced neointima formation and lumen stenosis. Quantitative PCR analysis revealed a blunted increase in senescence-associated proinflammatory changes in perivascular tissue compared to visceral adipose tissue and higher expression of mediators attenuating neointima formation. Elevated levels of protein inhibitor of activated STAT1 (PIAS1) and lower expression of STAT1- or NFκB-regulated genes involved in adipocyte differentiation, inflammation, and apoptosis/senescence were present in mouse PVAT, whereas PIAS1 was reduced in the PVAT of patients with atherosclerotic vessel disease. Our findings suggest that age affects adipose tissue and its paracrine vascular activities in a depot-specific manner. PIAS1 may mediate the age-independent vasculoprotective effects of perivascular fat.

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Section: Discussionmentioning

confidence: 55%

Age-Dependent and -Independent Effects of Perivascular Adipose Tissue and Its Paracrine Activities during Neointima Formation

Schütz

Gogiraju

Pavlaki

et al. 2019

IJMS

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“…However, as neointima proliferation, endothelial regeneration [44], and smooth muscle cells recruitment are dependent on alloimmune cellular responses [42] and involvement of hematopoietic stem cells [45], we have no evidence showing that the We can only speculate that our findings suggest that the susceptibility to transplant arteriosclerosis might be higher in ApoE-/-mice than in female Fisher rats [40], where neointimal lesions after syngeneic transplantation could not be detected. To elucidate these questions, a detailed study focused on transplant arteriosclerosis in syngeneic mice would be required, e.g.…”

Section: Lesions In the Transplanted Aorta Sections And Transplant Arcontrasting

confidence: 45%

“…The etiology of transplant arteriosclerosis was suggested to be multifactorial and its precise mechanism to date remains obscure [39]. In the rat, the severity of age-related neointima formation in syngeneic aorta transplantation (in the absence of alloreactivity and immunosuppressive drugs) is primarily determined by the recipient's age rather than the donor's age, with young recipients generally being less affected [40]. This complies with the fact that the lowest AFFVL in juvenile ApoE-/-mice was 60%, i.e.…”

Section: Lesions In the Transplanted Aorta Sections And Transplant Armentioning

confidence: 99%

Aorta transplantation in young apolipoprotein E-deficient mice: Possible model for studies on regression of atherosclerotic lesions?

Tonar¹,

Bobková

Witter

et al. 2010

Open Medicine

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AbstractSyngeneic transplantation of murine aorta segments with advanced atherosclerotic lesions in defined recipients is a valuable model for regression studies. To date, this model has not been used to study the regression of initial atherosclerotic lesions. The aim of this study was to evaluate a microsurgical technique of syngeneic heterotopic transplantation of the thoracic aorta of young apolipoprotein E-deficient (ApoE-/-) mice to the abdominal aorta of wild-type recipients. Stereological quantification methods were tested in order to assess changes in structure and volume of the aortic wall including the involvement of immune cells in changes of the atherosclerotic lesions. The animals were euthanised one month after surgery and histological analysis including stereological quantification of changes in both the grafts and adjacent aorta segments was performed. The overall survival rate of the recipients was 62.5%. No regression of initial atherosclerotic lesion was achieved and neointima formation and elastin degradation prevailed in all transplanted specimens. The volume of the arteriosclerotic lesions was higher (p<0.001) and elastin length density was lower (p<0.001) in transplanted ApoE-/- samples as compared to adjacent segments. In transplanted grafts, T- and B-lymphocytes, macrophages and neutrophilic granulocytes formed non-random clusters within the vessel wall and they were colocalised with the sutures. The reproducibility of the promising regression model was derogated in young mice by the striking dependence of the results upon the operation technique. Stereological assessment has proven to be accurate, correct and reproducible; it has provided us with robust quantitative estimates, which can be achieved with a reasonable effort.

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“…Thoracic aorta injury was performed by expansion of the artery with a balloon catheter as previously described. 14 Denudation of the endothelium was performed and verified properly by an in vivo Evans blue staining. 14 All protocols were approved by guidelines of Fudan University and conformed with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No.…”

Section: Animals and Balloon Expansion Injurymentioning

confidence: 99%

Ageing-exaggerated proliferation of vascular smooth muscle cells is related to attenuation of Jagged1 expression in endothelial cells

Zhou

Huang

et al. 2007

Cardiovascular Research

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Aging and Transplant Arteriosclerosis in Absence of Alloreactivity and Immunosuppressive Drugs in a Rat Aortic Model: Recipient Age???s Contribution

Cited by 5 publications

References 34 publications

Age-Dependent and -Independent Effects of Perivascular Adipose Tissue and Its Paracrine Activities during Neointima Formation

Age-Dependent and -Independent Effects of Perivascular Adipose Tissue and Its Paracrine Activities during Neointima Formation

Aorta transplantation in young apolipoprotein E-deficient mice: Possible model for studies on regression of atherosclerotic lesions?

Ageing-exaggerated proliferation of vascular smooth muscle cells is related to attenuation of Jagged1 expression in endothelial cells

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