HHcy and Ang II–Induced Aortic Aneurysm (p 1261)
Hyperhomocysteinemia is a causal risk factor for abdominal aortic aneurism, say Liu et al, and folic acid supplementation may help reduce that risk.
Abdominal aortic aneurism (AAA) is a leading cause of sudden death in older men. Risk factors for AAA include age, male gender, smoking and high-blood pressure. However, many AAA patients also have high blood levels of the amino acid homocysteine, leading to the suggestion that that hyperhomocysteinemia could be a contributing factor. Direct evidence implicating hyperhomocysteinemia has been lacking. But now, Liu et al report that addition of homocysteine to the drinking water of AAA-susceptible mice increased the likelihood that the animals would develop the condition. Histological analysis of the mice revealed the homocysteine caused inflammatory changes in the aorta. In vitro studies confirmed that homocysteine induced vessel wall fibroblasts to secrete proinflammatory cytokines and recruit monocytes and macrophages. In addition, the development of AAA was also retarded when the mice were fed folic acid, which promotes the breakdown of homocysteine. Based on these observations the authors suggest that folic acid supplements may help decrease the risk of AAA in humans.
Measurement of SNO Occupancy (p 1308)
Kohr et al have developed a new tool for measuring the extent of protein S-nitrosylation during myocardial preconditioning.
When a heart experiences a brief period of ischemia, it adapts to help protect against a subsequent and potentially more serious ischemic insult that could result in more extensive tissue damage. This adaptive process, which is known as myocardial preconditioning, is thought to involve, in part, the addition of nitric oxide to protein cysteine residues. This protein S-nitrosylation (SNO) prevents the oxidation and degradation of proteins—damage that might occur due to the release of reactive oxygen species during ischemia-reperfusion injury. The extent to which cardiac proteins are modified by SNO during preconditioning, however, was unknown. Kohr et al thus developed a technique whereby unmodified and modified cysteine residues of particular proteins are tagged and analyzed by mass spectrometry. Using this approach, they determined that a large number of proteins more than doubled their percentage of SNO-modified cysteines during experimental preconditioning of mouse hearts. These results confirm that SNO modification is an adaptive protective response and point to the usefulness of this tool in future preconditioning studies.
IL6 and IL10 in STEMI Patients (p 1336)
Ammirati et al find that the levels of cytokine IL-6 in heart attack survivors are indicative of long-term prognosis.
ST-elevation acute myocardial infarction (STEMI) is associated with high morbidity and mortality. It is currently believed that immunological factors influence not only the onset of a STEMI but also the extent of myocardial damage and prognosis. Interestingly, some STEMI patients have very high blood levels of the inflammatory cytokine IL6 while in other patients IL-6 levels remain low. Ammirati et al wondered why STEMI patients show such a difference. In their current study, they identified that patients with high IL6 tended to be older, have decreased blood levels of the “good” cholesterol, HDL, and have impaired coronary flow and left ventricle function at the time of discharge from hospital. They also tended to have a poorer prognosis—12 out of 109 patients with high IL6 died within 6 months of being discharged, while all 96 patients that had low IL6 were alive at 6 months. The best prognostic indication did not come from IL6 alone, however. Patients with high IL6 tended to have high levels of other cytokines, and the levels of two of these—1L10 and MIG—when combined with the level of IL6 offered the best prediction of patient outcome overall. Using this panel of cytokines might thus be an effective way to separate patients and identify those that need more close monitoring and more intensive treatment.
- © 2012 American Heart Association, Inc.