Monocyte Chemoattractant Protein-1 Expression in Aortic Tissues of Hypertensive Rats

Capers, Quinn; Alexander, R. Wayne; Lou, Pingping; León, Héctor De; Wilcox, Josiah N.; Ishizaka, Nobukazu; Howard, A. B.; Taylor, W. Robert

doi:10.1161/01.hyp.30.6.1397

Cited by 186 publications

(122 citation statements)

References 20 publications

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“…Similarly, we have shown that MCP-1 expression is upregulated in both an angiotensin II model and a norepinephrine model of hypertension. 4 It appears that even though both angiotensin II and wall strain may result in the upregulation of MCP-1 expression in vivo, the mechanoregulation of MCP-1 may be of greater importance under these experimental conditions. 18 The finding that macrophage recruitment represents a necessary requirement for the development of vascular hypertrophy provides strong support for the hypothesis that the vascular pathology of angiotensin II-induced hypertension, like atherosclerosis, occurs in part as the result of the development of an inflammatory state in the vascular wall.…”

Section: Discussionmentioning

confidence: 98%

CC Chemokine Receptor 2 Is Required for Macrophage Infiltration and Vascular Hypertrophy in Angiotensin II–Induced Hypertension

et al. 2000

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Abstract-Recent studies have identified the presence of macrophages in the arterial wall of hypertensive animals and suggested that as is the case in atherosclerosis, macrophage products may be important mediators of the adaptive response of the arterial wall. In support of this, we have previously shown that the expression of monocyte chemoattractant protein-1 is upregulated in the arteries of hypertensive animals. We hypothesized that macrophage recruitment is a critical step in the pathogenesis of hypertension. To obtain insights into this potential mechanism, we made use of mice deficient in the CC chemokine receptor 2 (CCR2), the receptor for monocyte chemoattractant protein-1. Hypertension was induced with the subcutaneous administration of angiotensin II (0.75 mg ⅐ kg Ϫ1 ⅐ d Ϫ1) for 7 days. Using in situ hybridization with a probe for c-fms to identify macrophages, we found that hypertension-induced macrophage infiltration of the arterial wall was virtually eliminated in CCR2-deficient mice. In addition, vascular hypertrophy was reduced by Ϸ65% compared with wild-type animals. These data demonstrate that CCR2 is essential for the recruitment of macrophages into the arterial wall in the setting of hypertension. Furthermore, the decreased hypertrophic response suggests that vascular hypertrophy occurs in part as a consequence of macrophage infiltration. In angiotensin II-induced hypertension, CCR2-mediated responses are critical to the process of macrophage recruitment and vascular hypertrophy and may represent one mechanism by which at least some forms of hypertension may lead to the development of atherosclerosis. (Hypertension. 2000;36:360-363.) Key Words: proteins Ⅲ angiotensin II Ⅲ hypertrophy Ⅲ macrophages I t is becoming increasingly apparent that hypertension, like atherosclerosis, is associated with the presence of an inflammatory response in the arterial wall. 1,2 The initial phase of this inflammatory response is characterized by the accumulation of macrophages in the arterial wall. [3][4][5] The importance of this macrophage infiltration in the development of hypertensive vasculopathy remains unknown. Furthermore, the precise factors that control macrophage recruitment into the vascular wall have not been determined.We recently demonstrated that the expression of monocyte chemoattractant protein-1 (MCP-1) is upregulated at both the message and protein level in aortic tissues of hypertensive animals. 4 This response was seen in animals made hypertensive with the infusion of either angiotensin II or norepinephrine. MCP-1 is a potent macrophage chemoattractant that has been previously implicated in the development of atherosclerosis. 6 -9 We hypothesized that in at least some forms of hypertension, MCP-1 upregulation and subsequent macrophage infiltration may represent a key step in the development of vascular hypertrophy. Implicit in this hypothesis is the assumption that vascular hypertrophy is dependent to a significant degree on the production of growth factors by resident macrophages.To gain ...

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Section: Discussionmentioning

confidence: 98%

CC Chemokine Receptor 2 Is Required for Macrophage Infiltration and Vascular Hypertrophy in Angiotensin II–Induced Hypertension

et al. 2000

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“…8 -10 Furthermore, in both angiotensin II and norepinephrine models of hypertension, expression of MCP-1 is upregulated in the aortic tissues. 10 This is associated with increased infiltration of the arterial wall with monocytes/macrophages. Mechanical strain applied to both endothelial and vascular smooth muscle cells results in an increase in the production of reactive oxygen species, 6,7 which have been implicated in the development of atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

“…An osmotic pump containing angiotensin II dissolved in a solution of 0.15 mol/L NaCl and 0.01N acetic acid at a concentration calculated to deliver Ϸ0.7 mg ⅐ kg Ϫ1 ⅐ d Ϫ1 of drug was inserted into a subcutaneous pocket. The dose of angiotensin II was selected on the basis of previous studies in our laboratories 10 and provides a plasma concentration of angiotensin II similar to that reported in patients with renovascular hypertension.…”

Section: Animals and Dietsmentioning

confidence: 99%

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Angiotensin II–Induced Hypertension Accelerates the Development of Atherosclerosis in ApoE-Deficient Mice

2001

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Background-Angiotensin II may contribute to the development and progression of atherosclerotic lesions because of its growth and proinflammatory effects. We sought to determine whether angiotensin II-induced hypertension would augment and accelerate the development of atherosclerotic lesions in apoE-deficient mice. Methods and Results-Angiotensin II (0.7 mg ⅐ kg Ϫ1 ⅐ d Ϫ1 SC) was administered to apoE-deficient mice via osmotic minipumps. The animals were placed on either standard chow or an atherogenic diet. After 8 weeks, the mean atherosclerotic lesion area in the descending thoracic and abdominal aortas of animals on a standard chow diet was 0.4Ϯ0.1% compared with 5.2Ϯ1.2% in those animals maintained on an atherogenic diet (PϽ0.0001). In angiotensin II-treated animals on standard chow, the mean lesion area was increased to 11.0Ϯ2.3%, which was further increased to 69.9Ϯ9.4% (PϽ0.0001) in angiotensin II-treated animals on an atherogenic diet. Similar findings were obtained when tissues from the ascending aorta were analyzed. At 8 weeks in mice receiving a standard chow diet, angiotensin II dramatically increased the atherosclerotic lesion area by 840Ϯ83 m 2 (PϽ0.0001). Animals on a high-fat diet had a similar marked increase in lesion area in response to angiotensin II (217Ϯ19 m 2 , PϽ0.0001). In contrast, when hypertension was induced with norepinephrine, only a modest effect on the atherosclerotic lesion area was observed. Conclusions-Angiotensin II-induced hypertension specifically increased the development of atherosclerosis in apoE knockout mice. This response was seen in animals receiving either standard chow or an atherogenic diet. These studies demonstrate the profound effect of angiotensin II on the development of atherosclerosis.

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“…Inhibition of angiotensin II by angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers attenuates the decline in renal function associated with diabetic and non-diabetic chronic kidney diseases (8,9,(16)(17)(18)(19). Monocyte chemoattractant protein-1 is an important chemoattractant for macrophages in a variety of kidney diseases (20), and its expression is induced by activation of the renin-angiotensin system (21,22). In an experimental model, monocyte chemoattractant protein-1 expression in kidneys was increased in hypertensive nephrosclerosis and was related to macrophage infiltration.…”

Section: A B C D Ementioning

confidence: 99%

Effects of Renin-Angiotensin System Blockade on Macrophage Infiltration in Patients with Hypertensive Nephrosclerosis

et al. 2007

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Monocyte Chemoattractant Protein-1 Expression in Aortic Tissues of Hypertensive Rats

Cited by 186 publications

References 20 publications

CC Chemokine Receptor 2 Is Required for Macrophage Infiltration and Vascular Hypertrophy in Angiotensin II–Induced Hypertension

CC Chemokine Receptor 2 Is Required for Macrophage Infiltration and Vascular Hypertrophy in Angiotensin II–Induced Hypertension

Angiotensin II–Induced Hypertension Accelerates the Development of Atherosclerosis in ApoE-Deficient Mice

Effects of Renin-Angiotensin System Blockade on Macrophage Infiltration in Patients with Hypertensive Nephrosclerosis

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