Plasma profiles of peripheral monocyte-related inflammatory markers in patients with arterial hypertension. Correlations with plasma endothelin-1.

BACKGROUND This study investigates the plasma activity of inflammatory mediators such as granulocyte-macrophage colony-stimulating factor (GM-CSF), C-C chemokines and soluble adhesion molecules, produced by monocyte-endothelial cell adhesive interaction, in patients with arterial hypertension. METHODS We studied 66 untreated patients with mild to moderate arterial hypertension (hypercholesterolemic: 34, normocholesterolemic: 32) and 30 sex- and age-matched normocholesterolemic normotensive controls. Plasma concentrations of GM-CSF, macrophage chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha), RANTES (regulated on activation normally T-cell expressed and secreted), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1), as well as plasma endothelin-1 (ET-1), were determined in study population by ELISA and RIA, respectively. RESULTS Hypertensives exhibited significantly higher levels of GM-CSF (6.5+/-1.3 vs. 2.3+/-0.7 pg/ml, P=0.099), MCP-1 (175+/-31 vs. 120+/-24 pg/ml, P=0.0093), MIP-1alpha (23+/-4 vs. 15+/-2 pg/ml, P=0.0089), RANTES (17+/-4 vs. 14+/-3 ng/ml, P=0.047), sICAM-1 (235+/-39 vs. 187+/-21 ng/ml, P=0.0041), sVCAM-1 (684+/-42 vs. 589+/-23 ng/ml, P=0.0045) and ET-1 (6.1+/-1.5 vs. 2.4+/-0.3 pg/ml, P=0.0095) than those of normotensives. The normocholesterolemic hypertensives had significantly lower levels of GM-CSF, MCP-1, MIP-1alpha, sICAM-1 and sVCAM-1 than hypercholesterolemic hypertensives but higher than normotensives. In hypertensives, ET-1 levels were significantly correlated with mean arterial pressure (r=0.51, P=0.028), MCP-1 values (r=0.45, P=0.047) and sICAM-1 levels (r=0.64, P=0.0090). Significant correlations were also found between LDL cholesterol values and plasma inflammatory factors GM-CSF (r=0.58, P=0.0088), MCP-1 (r=0.49, P=0.040) and sICAM-1 (r=0.53, P=0.034) in the hypercholesterolemic sub-group of hypertensives. CONCLUSIONS Inflammatory markers of monocyte-endothelial cell adhesive interaction are elevated in hypertensives in comparison to normotensives and may be related to plasma ET-1 activity. The coexistence of hypercholesterolemia may enhance this inflammatory process induced by arterial hypertension.

[1]  R. Levy,et al.  Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. , 1972, Clinical chemistry.

[2]  O. Carretero,et al.  The Loss of Endothelium‐Dependent Vascular Relaxation in Hypertension , 1986, Hypertension.

[3]  F. Incardona,et al.  Endothelin-1 induces production of the neutrophil chemotactic factor interleukin-8 by human brain-derived endothelial cells. , 1998, Blood.

[4]  G. Gibbons,et al.  Endothelium and Growth Factors in Vascular Remodeling of Hypertension , 1991, Hypertension.

[5]  The nature and action of granulocyte-macrophage colony stimulating factors. , 1980 .

[6]  A. Matsumori,et al.  Chemokines and cardiovascular diseases. , 2000, Cardiovascular research.

[7]  J. Parissis,et al.  Serum profiles of granulocyte-macrophage colony-stimulating factor and C-C chemokines in hypertensive patients with or without significant hyperlipidemia. , 2000, The American journal of cardiology.

[8]  A. J. Valente,et al.  Minimally modified low density lipoprotein induces monocyte chemotactic protein 1 in human endothelial cells and smooth muscle cells. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[9]  U. Ikeda,et al.  Involvement of adhesion molecules in human monocyte adhesion to and transmigration through endothelial cells in vitro. , 1994, Atherosclerosis.

[10]  E. Schiffrin.  Role of endothelin-1 in hypertension and vascular disease. , 2001, American journal of hypertension.

[11]  W. Frishman,et al.  Endothelin and endothelin antagonism: roles in cardiovascular health and disease. , 1995, American heart journal.

[12]  A. Dart,et al.  Lipids and the endothelium. , 1999, Cardiovascular research.

[13]  Q. Hamid,et al.  Chemokine- and cytokine-induced expression of endothelin 1 and endothelin-converting enzyme 1 in endothelial cells. , 2000, The Journal of allergy and clinical immunology.

[14]  M. Bell,et al.  Endothelin in coronary endothelial dysfunction and early atherosclerosis in humans. , 1995, Circulation.

[15]  G. Desideri,et al.  Early upregulation of endothelial adhesion molecules in obese hypertensive men. , 1999, Hypertension.

[16]  J. Kjekshus,et al.  Elevated circulating levels of C-C chemokines in patients with congestive heart failure. , 1998, Circulation.

[17]  S. Coughlin,et al.  Monocyte chemoattractant protein-1 in human atheromatous plaques. , 1991, The Journal of clinical investigation.

[18]  A. Blann,et al.  Circulating Endothelial Cell/Leukocyte Adhesion Molecules in Atherosclerosis , 1994, Thrombosis and Haemostasis.

[19]  G. Desideri,et al.  Early activation of vascular endothelium in nonobese, nondiabetic essential hypertensive patients with multiple metabolic abnormalities. , 1998, Diabetes.

[20]  A. Zeiher,et al.  Clinical importance of coronary endothelial vasodilator dysfunction and therapeutic options , 1999, Journal of internal medicine.

[21]  P. Vanhoutte,et al.  Endothelium-dependent responses in hypertension. , 1995, Hypertension research : official journal of the Japanese Society of Hypertension.

[22]  J. K. Lloyd,et al.  Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis , 1992, The Lancet.

[23]  T. Meinertz,et al.  Oxidative Stress Increases Endothelin‐1 Synthesis in Human Coronary Artery Smooth Muscle Cells , 2001, Journal of cardiovascular pharmacology.

[24]  P. Libby,et al.  Involvement of the immune system in human atherogenesis: current knowledge and unanswered questions. , 1991, Laboratory investigation; a journal of technical methods and pathology.

[25]  H. Krum,et al.  The effect of an endothelin-receptor antagonist, bosentan, on blood pressure in patients with essential hypertension. Bosentan Hypertension Investigators. , 1998, The New England journal of medicine.

[26]  R. Ross,et al.  Atherosclerosis is an inflammatory disease. , 1998, American heart journal.

[27]  U. Ikeda,et al.  Human monocyte-endothelial cell interaction induces synthesis of granulocyte-macrophage colony-stimulating factor. , 1996, Circulation.

[28]  G. Hansson.  Immune mechanisms in atherosclerosis. , 1989, Arteriosclerosis, thrombosis, and vascular biology.

[29]  L. Ghiadoni,et al.  Role of Endothelin in the Control of Peripheral Vascular Tone in Human Hypertension , 2001, Heart Failure Reviews.

[30]  P. Kligfield,et al.  Methods for detection of left ventricular hypertrophy: application to hypertensive heart disease. , 1993, European heart journal.

[31]  Monocyte Chemoattractant Protein-1 is Upregulated in Rats With Volume-Overload Congestive Heart Failure , 2000 .