SDF-1α (human)

Introduction: The inflammatory hypothesis of atherosclerosis is appealing in acute coronary syndromes, but the dynamics and precise role are not established. Objectives: The study investigates the levels of C reactive protein (CRP), interleukin 1β (IL-1β) and stromal-derived factor 1α (SDF-1α) at the time of acute myocardial infarction (AMI) and at 1 and 6 months afterwards, compared with a control group. Results: In the acute phase of AMI, CRP and SDF-1α were significantly higher, while IL-1β showed lower levels compared with controls. CRP positively correlated with coronary stenosis severity (rho = 0.3, p=.05) and negatively related with left ventricle ejection fraction (LVEF) at 1 month (rho= -0.43, p=.05). IL-1β weakly correlated with the severity of coronary lesions (rho =0.29, p=.02) and strongly with LVEF (rho= -0.8, p=.05). SDF-1α, slightly correlated with LVEF at 1 month (rho = 0.22, p=.01) and with the severity of coronary atherosclerosis (rho= -0.41, p=.003). Conclusions: CRP, IL-1β and SDF-1α have important dynamic in the first 6 months after AMI and CRP and SDF-1α levels correlated with the severity of coronary lesions and LVEF at 1 month after the acute ischaemic event.

The CXC chemokine CXCL12 is an important factor in physiological and pathological processes, including embryogenesis, hematopoiesis, angiogenesis and inflammation, because it activates and/or induces migration of hematopoietic progenitor and stem cells, endothelial cells and most leukocytes. Therefore, CXCL12 activity is tightly regulated at multiple levels. CXCL12 has the unique property of existing in six splice variants in humans, each having a specific tissue distribution and in vivo activity. Controlled splice variant transcription and mRNA stability determine the CXCL12 expression profile. CXCL12 fulfills its functions in homeostatic and pathological conditions by interacting with its receptors CXC chemokine receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3) and by binding to glycosaminoglycans (GAGs) in tissues and on the endothelium to allow a proper presentation to passing leukocytes. Homodimerizaton and heterodimerization of CXCL12 and its receptors can alter their signaling activity, as exemplified by the synergy between CXCL12 and other chemokines in leukocyte migration assays. Receptor binding may also initiate CXCL12 internalization and its subsequent removal from the environment. Furthermore, CXCL12 activity is regulated by posttranslational modifications. Proteolytic removal of NH2- or COOH-terminal amino acids, citrullination of arginine residues by peptidyl arginine deiminases or nitration of tyrosine residues reduce CXCL12 activity. This review summarizes the interactions of CXCL12 with the cellular environment and discusses the different levels of CXCL12 activity regulation.

Platelets are inflammatory anuclear cells with a well-established role in the development and manifestation of atherosclerosis. Activated platelets secrete a plethora of chemokines including CXCL4 or platelet factor 4 (PF4), CCL5, CXCL12 or stromal cell derived factor-1α (SDF-1α), CXCL16 and others, which initiate or promote local inflammatory processes at sites of vascular injury. These processes are mainly mediated by the recruitment of circulating haematopoietic stem cells, neutrophils, monocytes or lymphocytes on vascular wall. Under acute ischemic conditions platelet-derived chemokines may promote the mobilization of bone marrow-derived progenitor cells and their homing at lesion sites. This review focuses on the role of platelet-derived chemokines in inflammation and atherosclerosis. Further, we discuss the clinical value of plasma levels of chemokines in the prognosis of atherosclerotic heart disease.