Deregulated expression of monocyte chemoattractant protein-1 (MCP-1) in arterial hypertension: role in endothelial inflammation and atheromasia.
OBJECTIVE
Arterial hypertension is recurrently associated with inflammation of the endothelium as an effect of the upregulation of functional molecules, including cytokines, adhesion molecules and chemokines. However, the role of monocyte chemoattractant protein-1 (MCP-1) in maintaining the inflammatory state of endothelial cells (EC) that leads to the progressive cardiovascular damage is unclear.


METHODS
Here, we investigated the expression of MCP-1, its major cell source as well as recurrence of a defined polymorphism (-2518 MCP-1) apparently linked to endothelial damage in several diseases.


METHODS
Serum MCP-1 was measured by enzyme-linked immunosorbent assay (ELISA) in 740 hypertensive patients, subdivided according to their individual organ damage. Expression of both MCP-1 and its receptor CCR2 was evaluated in circulating ECs and macrophages by flow cytometry and real-time reverse transcriptase-polymerase chain reaction (RT-PCR), while gene variants of MCP-1 were revealed by PCR.


RESULTS
Soluble MCP-1 was significantly elevated in patients with diffuse atheromasia. Furthermore, it was overexpressed by ECs activated to attract macrophages via the MCP-1/CCR2 pathway, whereas the -2518 MCP-1 polymorphism was correlated with atherosclerosis in most patients. CONCLUSIONS.: Overexpression of MCP-1 is predominant in hypertensive patients with atheromasia in the form of a defined polymorphism. Measurement of MCP-1 may thus reflect the degree of endothelial damage, while early detection of such a polymorphism may acquire a prognostic value in the development of atherosclerosis.
Tucci
Marco
M
DIMO, Department of Internal Medicine and Clinical Oncology, University of Bari, Italy. m.tucci@dimo.uniba.it
Quatraro
Cosima
C
Frassanito
Maria Antonia
MA
Silvestris
Franco
F
D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000097:blood; D018932:Chemokine CCL2 / Q000097:blood* / Q000235:genetics; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000503:physiopathology; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D045726:Metalloproteases / Q000378:metabolism; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics* / Q000502:physiology; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000378:metabolism; D018709:Statistics, Nonparametric; D014657:Vasculitis / Q000097:blood*
C111835:CCL2 protein, human; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D045726:Metalloproteases