CC Chemokine Ligand-5 (CCL5/RANTES) and CC Chemokine Ligand-18 (CCL18/PARC) Are Specific Markers of Refractory Unstable Angina Pectoris and Are Transiently Raised During Severe Ischemic Symptoms

Abstract

Background-Chemokines play an important role in atherogenesis and in ischemic injury and repair; however, prospective data on individual chemokines in unstable angina pectoris (UAP) are scarce. Therefore, we assessed chemokine patterns in a prospective cohort of patients with UAP. Methods and Results-Plasma samples of 54 patients with Braunwald class IIIB UAP were examined at baseline for 11 chemokines and 5 inflammatory mediators via multiplex analysis. Levels of CC chemokine ligand (CCL)-5 (also known as RANTES [regulated on activation, normally T-cell expressed, and secreted]; 32.7 versus 23.1 ng/mL, Pϭ0.018) and CCL18 (also known as PARC [pulmonary and activation-regulated chemokine]; 104.4 versus 53.7 ng/mL, Pϭ0.011) were significantly elevated in patients with refractory ischemic symptoms versus stabilized patients. Temporal monitoring by ELISA of CCL5, CCL18, and soluble CD40 ligand (sCD40) levels revealed a drop in CCL5 and sCD40L levels in all UAP patients from day 2 onward (CCL5 12.1 ng/mL, PϽ0.001; sCD40L 1.35 ng/mL, PϽ0.05), whereas elevated CCL18 levels were sustained for at least 2 days, then were decreased at 180 days after inclusion (34.5 ng/mL, PϽ0.001). Peripheral blood mononuclear cells showed increased protein expression of chemokine receptors CCR3 and CCR5 in CD3 ϩ and CD14 ϩ cells at baseline compared with 180 days after inclusion, whereas mRNA levels were downregulated, which was attributable in part to a postischemic release of human neutrophil peptide-3-positive neutrophils and in part to negative feedback. Finally, elevated CCL5 and CCL18 levels predicted future cardiovascular adverse events, whereas C-reactive protein and sCD40L levels did not. Conclusions-We are the first to report that CCL18 and CCL5 are transiently raised during episodes of UAP, and peak levels of both chemokines are indicative of refractory symptoms. Because levels of both chemokines, as well as of cognate receptor expression by circulating peripheral blood mononuclear cells, are increased during cardiac ischemia, this may point to an involvement of CCL5/CCL18 in the pathophysiology of UAP and/or post-UAP responses.

Menopause and Ovariectomy Cause a Low Grade of Systemic Inflammation that May Be Prevented by Chronic Treatment with Low Doses of Estrogen or Losartan

“…With regard to RANTES, in our study there are clear species differences in the RANTES pattern between postmenopausal women and ovariectomized rats. In this context, the circulating RANTES levels in humans are higher than those in rodents (nanogram range vs picogram range) (29,30). Additionally, since it is now well known that platelets store RANTES in their ␣-granules and release it during acute stages of inflammation (31)(32)(33), it is also possible that the number of circulating platelets or the amount of RANTES stored in them differs between humans and rats.…”

NADPH Oxidases Regulate CD44 and Hyaluronic Acid Expression in Thrombin-treated Vascular Smooth Muscle Cells and in Atherosclerosis

“…In concurrence with our results, Bae et al (67) have recently reported that RANTES is regulated in a NADPH oxidase-dependent manner. Furthermore, a transient increase in RANTES levels was reported in patients experiencing unstable angina pectoris (68). TNF-␣ plays a key role in the inflammatory cascade associated with atherosclerosis (69) and several studies support the association of increased TNF-␣ levels with increased risk of myocardial infarction (70,71).…”

Pretreatment with a combination of ligustrazine and berberine improves cardiac function in rats with coronary microembolization

“…IL-1β increases dynamically following CME and is associated with impaired cardiac function [37] . RANTES has been identified as a specific marker for unstable angina pectoris by several studies [38][39] . The adhesion molecule, ICAM-1, also represents a marker of slow coronary flow caused by microvascular dysfunction [40][41] .…”