Building an understanding of the mechanisms of atherosclerosis leading to myocardial infarction

Kurata and his team have set about developing understanding on rupture-prone plaques in order to benefit acute coronary syndrome (ACS) patients. It was already known that the characteristics of rupture-prone vulnerable plaques include a thin fibrous cap and a large lipid core. 'It has also been suggested that cytokines released from the lipid core play major roles in plaque vulnerability,' says Kurata. However, he was aware that a cause-and-effect relationship supported by animal or human data was lacking, and proposed that smooth muscle cells in the fibrous cap played a major role. The team obtained stenotic coronary arteries from the autopsy material of 51 adults and divided the cases into three groups: those who had died from ACS, those with a past history of ACS but had died from other causes, and those with no history of ACS. 'We measured a range of histological data, including fibrous cap and lipid core in each specimen, and performed immunohistochemistry for alpha-smooth muscle actin (à-SMA) and h-caldesmon. We also counted the ratio of h-caldesmon(+) cells to à-SMA(+) cells in the neointima,' outlines Kurata. 'We found that there was a decreased positivity of h-caldesmon in neointimal smooth muscle cells in ACS cases,' Kurata continues. This is indicative of a more immature phenotype and could well be associated with plaque vulnerability that promotes ACS. He is particularly pleased with the results from this investigation. 'In the results of immunohistochemistry of coronary and carotid artery, the ratio of h-caldesmon+ cells to à-SMA+ smooth muscle cells in the intima was not different between the plaque side and the opposite side of the artery in the same person,' says Kurata. 'This means that maturity of intimal smooth muscle cells indicated by this ratio was not influenced by cytokines produced by lipid core.' It appears that the immaturity of intimal smooth cells is a cause - not a result - of plaque vulnerability; if the immaturity is affected by plaque then the opposite should be relatively mature.