Cardiac isoform of alpha 2 macroglobulin and its reliability as a cardiac marker in HIV patients.

BACKGROUND: Cardiac isoform of alpha 2 macroglobulin (CA2M), a serum protein (182000Mr) has been used as a diagnostic molecular marker for cardiac manifestations in HIV and diabetic patients. This study investigates the reliability of CA2M as an early diagnostic marker for cardiac manifestations in HIV patients and factors that could possibly influence their levels. METHODS: A total of 206 serum samples were analysed from HIV patients with cardiac diseases (68), with non-cardiac ailments (48), opportunistic infections (34) and without other co-morbidities (56). The immuno-cross-reactivity between human serum CA2M and anti-rat CA2M antibody was tested and quantified by sandwich enzyme linked immunosorbent assay (ELISA). RESULTS: The CA2M levels were high in HIV patients with cardiac diseases irrespective of the manifestations. The CA2M levels were not influenced by opportunistic infections, non-cardiac ailments and patient parameters like age, sex, duration of illness, past history of other co-morbidities. CONCLUSION: CA2M can be used as a reliable early diagnostic marker in HIV patients with cardiac manifestations. CA2M levels were not influenced by other patient parameters.

Identification of novel inhibitors of dietary lipid absorption using zebrafish.

Pharmacological inhibition of dietary lipid absorption induces favorable changes in serum lipoprotein levels in patients that are at risk for cardiovascular disease and is considered an adjuvant or alternative treatment with HMG-CoA reductase inhibitors (statins). Here we demonstrate the feasibility of identifying novel inhibitors of intestinal lipid absorption using the zebrafish system. A pilot screen of an unbiased chemical library identified novel compounds that inhibited processing of fluorescent lipid analogues in live zebrafish larvae. Secondary assays identified those compounds suitable for testing in mammals and provided insight into mechanism of action, which for several compounds could be distinguished from ezetimibe, a drug used to inhibit cholesterol absorption in humans that broadly inhibited lipid absorption in zebrafish larvae. These findings support the utility of zebrafish screening assays to identify novel compounds that target complex physiological processes.