Major histocompatibility complex class II antigen expression is suppressed by estradiol in cardiac allografts

Lou, Hong; Kodama, Teruaki; Wang, Y.N.; Katz, Nevin M.; Ramwell, Peter W.; Foegh, Marie L.

doi:10.1016/s0041-1345(97)00534-4

Cited by 4 publications

(2 citation statements)

References 3 publications

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“…27 The present study confirms that hypercholesterolemia increases the prevalence of early intimal lesions in the transplanted hearts; this has been documented 4 weeks after implantation in cholesterol-fed animals. 28,29 Acceleration of the proliferative vascular damage by a factor of 3 to 4 is seen with cholesterol feeding, but frequency or severity of lesions is unchanged in chronically rejecting rat aortic allografts in the absence of hypertriglyceridemia 30 and in apoE-deficient recipients of allotransplants. 31 Cholesterol feeding has a limited effect on normal arteries, as shown in coronary arteries of control and native hypercholesterolemic animals.…”

Section: Intimal Hyperplasiamentioning

confidence: 99%

Hypercholesterolemia Increases Coronary Endothelial Dysfunction, Lipid Content, and Accelerated Atherosclerosis After Heart Transplantation

Perrault

Mahlberg

Breugnot

et al. 2000

ATVB

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Abstract-Hyperlipidemia may increase endothelial damage and promote accelerated atherogenesis in graft coronary vasculopathy. To study the effects of hypercholesterolemia on coronary endothelial dysfunction, intimal hyperplasia, and lipid content, a porcine model of heterotopic heart transplantation, allowing nonacute rejection without immunosuppressive drugs, was used. A high cholesterol diet was fed to donor and recipient swine 1 month before and after transplantation. The endothelial function of coronary arteries of native and transplanted hearts from cholesterol-fed animals was studied in organ chambers 30 days after implantation and compared with endothelial function in arteries from animals fed a normal diet. The total serum cholesterol increased 3-fold in donors and recipients. Endotheliumdependent relaxations to serotonin, to the ␣ 2 -adrenergic agonist UK14,304, and to the direct G-protein activator sodium fluoride were decreased significantly in allografted hearts compared with native hearts from both groups. Relaxations to the calcium ionophore A23187 and bradykinin were decreased significantly in allografts from animals fed the high cholesterol diet. The prevalence of intimal hyperplasia was significantly increased in coronary arteries from hypercholesterolemic swine. There was a significant increase in the lipid content of allograft arteries of hypercholesterolemic recipients. Hypercholesterolemia causes a general coronary endothelial dysfunction, increases the prevalence of intimal hyperplasia, and augments the incorporation of lipids in the vascular wall after heart transplantation. Hyperlipidemia accelerates graft coronary atherosclerosis through its effects on the endothelium. Key Words: endothelium Ⅲ lipids Ⅲ coronary arteries Ⅲ transplantation Ⅲ atherosclerosis T he normal endothelium contributes to the local regulation of vasomotor tone and the maintenance of a nonthrombogenic surface, acts as a selective barrier controlling permeability and transport, and regulates the adhesion and extravasation of neutrophils, monocytes, and lymphocytes 1 and the proliferation of underlying vascular smooth muscle cells. These properties are due to the ability of endothelial cells to secrete endothelium-derived relaxing factors such as nitric oxide, endothelium-derived hyperpolarizing factor, and prostacyclin. 2 Endothelial dysfunction is a fundamental initial step in the progression of atherosclerosis.Although heart transplantation remains the treatment of choice for medically unresponsive terminal heart disease and is associated with a 5-year survival of Ϸ70%, coronary graft vasculopathy develops in a majority of transplant recipients and is the main cause of death beyond the first year after transplantation. 3 Accelerated atherosclerosis is preceded by reduced dilatation of the coronary artery to endotheliumdependent agonists. 4 This endothelial dysfunction is due to an immunologic injury directed at the endothelial cells and to other factors that cause endothelial activation and trigger a cascade of path...

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Section: Intimal Hyperplasiamentioning

confidence: 99%

Hypercholesterolemia Increases Coronary Endothelial Dysfunction, Lipid Content, and Accelerated Atherosclerosis After Heart Transplantation

Perrault

Mahlberg

Breugnot

et al. 2000

ATVB

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“…70 Importantly, dietary L-arginine has been shown to attenuate the structural changes of transplant vasculopathy in vivo associated with downregulation of insulin-like growth factor-I and interleukin-6. 71 The literature supports a protective role for eNOS. In a murine chronic-rejection model, transplant atherosclerosis is accelerated in aortic allografts of eNOS-deficient mice.…”

Section: Does No Deficiency Play a Role In The Progression Of Transplmentioning

confidence: 98%

Cardiac Allograft Vasculopathy and Dysregulation of the NO Synthase Pathway

Weis

Cooke

2003

ATVB

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Abstract-Cardiac allograft vasculopathy is the most aggressive form of atherosclerosis in humans and is the leading cause of death after the first year of heart transplantation. Endothelial dysfunction is a major contributing factor to the acceleration of coronary vascular disease in these individuals. A reflection of this endothelial dysfunction is the severe impairment in endothelium-dependent vasodilation that occurs early after transplantation. The etiology of this allograft endothelial alteration is multifactorial and may include preexisting atherosclerosis of the graft vessels, reperfusion injury during transplantation, denervation, disruption of the lymphatic system, and acute and chronic immune injury, as well as traditional risk factors for coronary artery disease (hyperlipidemia, diabetes, hypertension, or hyperhomocysteinemia) and pathogens, such as cytomegalovirus. The alteration in endothelial function affects vasomotor tone of the coronary arteries. Evidence indicates that there may be an impairment of endothelial production and/or activity of NO. Because NO is a potent vasodilator, its deficiency would explain the abnormal vasomotor tone in these individuals. In addition, because NO inhibits key processes in vascular inflammation and atherosclerosis, its absence may contribute to the acceleration of transplant vascular disease. Recent studies from our group and others have shed light on the mechanisms of endothelial dysfunction and its importance in cardiac allograft vasculopathy. In addition, the alteration in endothelial function contributes to vascular inflammation and progression of the disease. Key Words: endothelium Ⅲ coronary Ⅲ transplantation Ⅲ heart Ⅲ inflammation A ccelerated graft atherosclerosis is a key feature of most chronic rejection syndromes. 1 Coronary atherosclerosis frequently limits the long-term success of cardiac transplantation, is characterized by intimal proliferation during the early phase of the disease, and ultimately manifests itself as luminal stenosis of epicardial branches, occlusion of smaller vessels, and myocardial infarction. 2 The most salient difference between cardiac allograft vasculopathy (CAV) and typical atherosclerotic coronary artery disease is the diffuse involvement of the coronary vasculature. 3 Whereas the structural changes of atherosclerosis largely affect the proximal epicardial coronary arteries, in CAV, the disease is much more extensive. Cardiac transplant recipients often manifest concentric intimal thickening that affects the distal epicardial vessels, as well as their branches. Intimal thickening and inflammation may extend into the donor aorta up to the suture lines and, in some instances, even into the great veins of the allograft. 4,5 Histopathologic analysis reveals that morphological manifestation of this vasculopathy may range from concentric, diffuse, intimal hyperplasia to fibrofatty plaques indistinguishable from spontaneously occurring atherosclerosis. 3 The clinical detection of CAV is made more difficult by the frequent absenc...

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Expression of estrogen receptor sub-types α and β in acute and chronic cardiac allograft vasculopathy

Savolainen

Frösén

Petrov

et al. 2001

The Journal of Heart and Lung Transplantation

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Major histocompatibility complex class II antigen expression is suppressed by estradiol in cardiac allografts

Cited by 4 publications

References 3 publications

Hypercholesterolemia Increases Coronary Endothelial Dysfunction, Lipid Content, and Accelerated Atherosclerosis After Heart Transplantation

Hypercholesterolemia Increases Coronary Endothelial Dysfunction, Lipid Content, and Accelerated Atherosclerosis After Heart Transplantation

Cardiac Allograft Vasculopathy and Dysregulation of the NO Synthase Pathway

Expression of estrogen receptor sub-types α and β in acute and chronic cardiac allograft vasculopathy

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