CXC chemokine KC fails to induce neutrophil infiltration and neoangiogenesis in a mouse model of myocardial infarction.

Background: Chemokines and neutrophils, known as important players in the inflammatory cascade, also contribute to heart tissue recovery and scar formation after myocardial infarction (MI). The objective of this study was to determine the importance of ELR-containing CXC chemokine KC in neutrophil infiltration and neoangiogenesis, in a mouse model of chronic MI.

Methods And Results: MI was induced in mice divided in four groups: control (untreated), anti-KC "later" (anti-KC antibody injections started 4 days after MI and then delivered every 72 hours for 3 weeks, to inhibit angiogenesis), anti-KC "earlier" (anti-KC antibody injections 1 day before and 1 day after MI, to block neutrophil infiltration), anti-KC (anti-KC antibody injections 1 day before and 1 day after MI, and then every 72 hours for 3 weeks).

Contribution of platelet CX(3)CR1 to platelet-monocyte complex formation and vascular recruitment during hyperlipidemia.

Objective: The chemokine receptor CX(3)CR1 is an inflammatory mediator in vascular diseases. On platelets, its ligation with fractalkine (CX(3)CL1) induces platelet activation followed by leukocyte recruitment to activated endothelium. Here, we evaluated the expression and role of platelet-CX(3)CR1 during hyperlipidemia and vascular injury.

Repair after myocardial infarction, between fantasy and reality: the role of chemokines.

Despite considerable progress over the last decades, acute myocardial infarction continues to remain the major cause of morbidity and mortality worldwide. The present therapies include only cause-dependent interventions, which are not able to reduce myocardial necrosis and optimize cardiac repair following infarction. This review highlights the cellular and molecular processes after myocardial injury and focuses on chemokines, the main modulators of the inflammatory and reparatory events, as the most valuable drug targets.

Exploring HCN channels as novel drug targets.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have a key role in the control of heart rate and neuronal excitability. Ivabradine is the first compound acting on HCN channels to be clinically approved for the treatment of angina pectoris. HCN channels may offer excellent opportunities for the development of novel anticonvulsant, anaesthetic and analgesic drugs.

Chemokines: inflammatory mediators of atherosclerosis.

Atherosclerosis as the underlying mechanisms of myocardial infarction, stroke and peripheral artery disease remains the major cause of morbidity and mortality in developed countries. Recent developments in vascular biology have indicated that atherosclerosis can be best characterized as a chronic inflammatory disease of the vessel wall that promotes lesion development and progression. Chemokines regulate and control these processes by orchestrating adhesive interactions of circulating blood cells with the arterial wall and their subsequent extravasation.

Stereospecific and redox-sensitive increase in monocyte adhesion to endothelial cells by homocysteine.

Objective: Previous studies have shown that elevated homocysteine (Hcy) levels promote the development of atherosclerotic lesions in atherosclerosis-prone animal models. There is evidence that oxidant stress contributes to Hcy's deleterious effects on the vasculature. The accumulation and adhesion of monocytes to the vascular endothelium is a critical event in the development of atherosclerosis.

Influence of hyperhomocysteinemia on the cellular redox state--impact on homocysteine-induced endothelial dysfunction.

Hyperhomocysteinemia is an independent risk factor for the development of atherosclerosis. An increasing body of evidence has implicated oxidative stress as being contributory to homocysteine's deleterious effects on the vasculature. Elevated levels of homocysteine may lead to increased generation of superoxide by a biochemical mechanism involving nitric oxide synthase, and, to a lesser extent, by an increase in the chemical oxidation of homocysteine and other aminothiols in the circulation.