Risky communication in atherosclerosis and thrombus formation

Atherosclerosis, a progressive disease of medium- and large-sized arteries, constitutes the major cause of death in developed countries, and is becoming increasingly prevalent in developing countries as well. The main consequences of atherosclerosis are myocardial infarction, cerebral infarction and aortic aneurysm. This inflammatory disease is characterised by specific intimal lesions where lipids, leukocytes and smooth muscle cells accumulate in the arterial wall over time. Risk factors for atherosclerosis can mainly be divided into two groups: i) risk factors induced by environment and behaviour (e.g., Western diet, smoking and sedentary lifestyle) and ii) genetic risk factors. Multiple epidemiological studies have associated a single nucleotide polymorphism (SNP) in the GJA4 gene, coding for connexin37 (Cx37), with increased risk for atherosclerosis and myocardial infarction. Connexins form gap junctions or hemi-channels that mediate an exchange of factors between i) the cytosol of two adjacent cells or ii) the cytosol and the extracellular environment, respectively. The GJA4 SNP codes for a proline-to-serine substitution at amino acid 319 in the regulatory C-terminus of the Cx37 protein, thereby altering basic and regulatory properties of its gap junction- and hemi-channels. In this review we discuss current evidence for mechanisms that link the GJA4 SNP to atherosclerosis or thrombus formation after plaque rupture.