The role of hypertension in hemodialysis-associated atherosclerosis

Vincenti, Flavio; Amend, W; Abele, John S.; Feduska, Nicholas J.; Salvatierra, Oscar

doi:10.1016/0002-9343(80)90104-7

Cited by 201 publications

(58 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although structural and functional abnormalities of the heart (2-5) and stiffness of the large arteries as a result of changes in the arterial media (6,7) may play a role, there are several observations that are compatible with the idea that increased atherosclerosis also contributes to the increased cardiovascular mortality. Angiographic studies of small series of patients considered for renal transplantation (8,9) and histologic evaluations of arterial biopsies from renal transplant recipients (10,11) have suggested that the prevalence of atherosclerosis might be higher in uremic compared with nonuremic individuals. Also, chronic renal failure (CRF) enhances a number of well-established risk factors for atherosclerosis (e.g., BP, plasma levels of atherogenic lipoproteins (12)) and affects several additional factors that potentially promote atherogenesis (e.g., homocysteine metabolism (13), inflammatory mediators (14,15), the balance between oxidants and antioxidants (16), plasma concentrations of advanced glycation end products [AGE] (17)).…”

mentioning

confidence: 99%

Chronic Renal Failure Accelerates Atherogenesis in Apolipoprotein E–Deficient Mice

Bro

Bentzon²,

Falk³

et al. 2003

Journal of the American Society of Nephrology

140

116

View full text Add to dashboard Cite

Abstract. Cardiovascular mortality is 10 to 20 times increased in patients with chronic renal failure (CRF). Risk factors for atherosclerosis are abundant in patients with CRF. However, the pathogenesis of cardiovascular disease in CRF remains to be elucidated. The effect of CRF on the development of atherosclerosis in apolipoprotein E-deficient male mice was examined. Seven-week-old mice underwent 5/6 nephrectomy (CRF, n ϭ 28), unilateral nephrectomy (UNX, n ϭ 24), or no surgery (n ϭ 23). Twenty-two weeks later, CRF mice showed increased aortic plaque area fraction (0.266 Ϯ 0.033 versus 0.045 Ϯ 0.006; P Ͻ 0.001), aortic cholesterol content (535 Ϯ 62 versus 100 Ϯ 9 nmol/cm 2 intimal surface area; P Ͻ 0.001), and aortic root plaque area (205,296 Ϯ 22,098 versus 143,662 Ϯ 13,302 m 2 ; P Ͻ 0.05) as compared with no-surgery mice; UNX mice showed intermediate values. The plaques from uremic mice contained CD11b-positive macrophages and showed strong staining for nitrotyrosine. Systolic BP and plasma homocysteine concentrations were similar in uremic and nonuremic mice. Plasma urea and cholesterol concentrations were elevated 2.6-fold (P Ͻ 0.001) and 1.5-fold (P Ͻ 0.001) in CRF compared with no-surgery mice. Both variables correlated with aortic plaque area fraction (r 2 ϭ 0.5, P Ͻ 0.001 and r 2 ϭ 0.3, P Ͻ 0.001, respectively) and with each other (r 2 ϭ 0.5, P Ͻ 0.001). On multiple linear regression analysis, only plasma urea was a significant predictor of aortic plaque area fraction. In conclusion, the present findings suggest that uremia markedly accelerates atherogenesis in apolipoprotein E-deficient mice. This effect could not be fully explained by changes in BP, plasma homocysteine levels, or total plasma cholesterol concentrations. Thus, the CRF apolipoprotein E-deficient mouse is a new model for studying the pathogenesis of accelerated atherosclerosis in uremia.

show abstract

mentioning

confidence: 99%

Chronic Renal Failure Accelerates Atherogenesis in Apolipoprotein E–Deficient Mice

Bro

Bentzon²,

Falk³

et al. 2003

Journal of the American Society of Nephrology

140

116

View full text Add to dashboard Cite

show abstract

“…Uremic patients have impaired endothelium-dependent vasodilation (4) and increased arterial stiffness (5). Histologic examinations of arterial biopsies from uremic patients have shown atherosclerosis-like lesions in the intima as wells as medial calcifications (6,7). Recently, independent results from three groups (including ours) have established that nephrectomy-induced uremia confers markedly accelerated formation of intimal atherosclerosis-like lesions in mice with genetical hyperlipidemia (i.e., apolipoprotein-Edeficient [apo-EϪ/Ϫ] mice) (8 -10).…”

mentioning

confidence: 99%

Increased Expression of Adhesion Molecules in Uremic Atherosclerosis in Apolipoprotein-E–Deficient Mice

Bro¹,

Moeller²,

Andersen

et al. 2004

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Abstract. Chronic renal failure markedly accelerates atherosclerosis in apolipoprotein-E-deficient mice, but the mechanism is unknown. The recruitment of inflammatory cells in the arterial wall by vascular adhesion molecules plays a key role in the formation of classical atherosclerosis. This study examines whether the expression of vascular adhesion molecules is increased in uremic atherosclerosis. Uremia was induced by 5/6 nephrectomy; control mice were sham-operated. After 2 wk of uremia, no lesion formation could be demonstrated in uremic or control mice. After 12 wk, aortas from uremic mice had a 9.8-fold increase of the aortic plaque area fraction compared with control mice (P Ͻ 0.0001). The aortic expression of intercellular adhesion molecule-1 (ICAM-1) mRNA in uremic mice was 215 Ϯ 31% (P Ͻ 0.05) and 243 Ϯ 55% (P Ͻ 0.05) of that in controls after 2 and 12 wk, respectively (n ϭ 9 ϫ 4). In contrast, aortic expression of vascular cell adhesion molecule-1 (VCAM-1) mRNA in uremic mice was unchanged after 2 wk but increased to 237 Ϯ 40% (P Ͻ 0.01) of that in control mice after 12 wk. On immunohistochemistry of aortas from uremic mice, ICAM-1 was predominantly present in endothelial cells both in nonlesioned and lesioned aortas, whereas VCAM-1 was predominantly present in the medial smooth muscle cell layer in lesioned aortas. The plasma concentration of soluble ICAM-1 (sICAM-1) (but not of sVCAM-1) was slightly elevated after 2 wk of uremia. In contrast, both sICAM-1 and sVCAM-1 plasma concentrations were markedly higher in uremic than control mice after 12 wk. These results suggest that uremic atherosclerosis is preceded by an upregulation of ICAM-1 expression in arterial endothelium and that formation of early uremic lesions is accompanied by upregulation of VCAM-1 expression in the medial smooth muscle cell layer.

show abstract

“…This is probably because of the generalized effects of prolonged systemic pathology in multiple organs before they entered dialytic treatment [13]. Some studies suggested a clear relationship between blood pressure and atherosclerosis [14]. In the present study, the maintenance group contained many hypertensive patients, and this suggested that prolonged hypertension was important for the development of atherosclerosis.…”

Section: General Risk Factorsmentioning

confidence: 50%

Clinical Characteristics and Survival in End-Stage Renal Disease Patients with Arteriosclerosis obliterans

Nakamura

Sasaki²,

Nakahama³

et al. 2002

Am J Nephrol

View full text Add to dashboard Cite

Background: Atherosclerotic disease (ASO) is considered a serious problem in dialysis patients. We tried to clarify the characteristics of ASO and to evaluate its impact on survival. Methods: Between January 1990 and December 1999, 525 patients with end-stage renal disease were admitted to our hospital. Among these patients, 71 (59 male and 12 female) had ASO. Blood pressure and blood samples were measured before and after hemodialysis, and were compared with the hemodialysis patients without any cardiovascular diseases. Mortality findings were collected until April 30, 2000. Results: Patients with ASO contained a larger percentage of males, hypertension, hyperlipidemia, diabetes mellitus, nephrosclerosis and smoking status. Their serum calcium, serum phosphate, triglyceride and C-reactive protein levels were also higher. During the follow-up period (2.8 ± 0.2 years), the mortality rate of the patients with ASO was higher than the hemodialysis patients without any cardiovascular diseases. Among the patients with ASO, the significant covariates concerning the cardiovascular mortality rate were age, hyperlipidemia and smoking status according to the Cox Proportional Hazards regression analysis. Conclusions: Hemodialysis patients with ASO had many traditional risk factors and uremic risk factors. Their survival rate was poorer and dependent on these risk factors.

show abstract

The role of hypertension in hemodialysis-associated atherosclerosis

Cited by 201 publications

References 16 publications

Chronic Renal Failure Accelerates Atherogenesis in Apolipoprotein E–Deficient Mice

Chronic Renal Failure Accelerates Atherogenesis in Apolipoprotein E–Deficient Mice

Increased Expression of Adhesion Molecules in Uremic Atherosclerosis in Apolipoprotein-E–Deficient Mice

Clinical Characteristics and Survival in End-Stage Renal Disease Patients with Arteriosclerosis obliterans

Contact Info

Product

Resources

About