Statins: More than Cholesterol Reduction

This article contains information from a talk given by the author at the RMS on 14/01/03, entitled: Statins and Immuno-modulation: A New Frontier. Statins represent one of the major successes of cardiology in the secondary prevention of coronary artery disease. This article attempts to understand the very molecule which makes many quake in their boots, cholesterol, and how basic science research continues to find novel methods in which statin therapy can participate

Small diameter helical vascular scaffolds support endothelial cell survival.

There is an acute clinical need for small-diameter vascular grafts as a treatment option for cardiovascular disease. Here, we used an intelligent design system to recreate the natural structure and hemodynamics of small arteries. Nano-fibrous tubular scaffolds were fabricated from blends of polyvinyl alcohol and gelatin with inner helices to allow a near physiological spiral flow profile, using the electrospinning technique. Human coronary artery endothelial cells (ECs) were seeded on the inner surface and their viability, distribution, gene expression of mechanosensitive and adhesion molecules compared to that in conventional scaffolds, under static and flow conditions. We show significant improvement in cell distribution in helical vs. conventional scaffolds (94% ± 9% vs. 82% ± 7.2%; P < 0.05) with improved responsiveness to shear stress and better ability to withhold physiological pressures. Our helical vascular scaffold provides an improved niche for EC growth and may be attractive as a potential small diameter vascular graft

Prognostic implications of troponin T variations in inherited cardiomyopathies using systems biology.

The cardiac troponin T variations have often been used as an example of the application of clinical genotyping for prognostication and risk stratification measures for the management of patients with a family history of sudden cardiac death or familial cardiomyopathy. Given the disparity in patient outcomes and therapy options, we investigated the impact of variations on the intermolecular interactions across the thin filament complex as an example of an unbiased systems biology method to better define clinical prognosis to aid future management options. We present a novel unbiased dynamic model to define and analyse the functional, structural and physico-chemical consequences of genetic variations among the troponins. This was subsequently integrated with clinical data from accessible global multi-centre systematic reviews of familial cardiomyopathy cases from 106 articles of the literature: 136 disease-causing variations pertaining to 981 global clinical cases. Troponin T variations showed distinct pathogenic hotspots for dilated and hypertrophic cardiomyopathies; considering the causes of cardiovascular death separately, there was a worse survival in terms of sudden cardiac death for patients with a variation at regions 90-129 and 130-179 when compared to amino acids 1-89 and 200-288. Our data support variations among 90-130 as being a hotspot for sudden cardiac death and the region 131-179 for heart failure death/transplantation outcomes wherein the most common phenotype was dilated cardiomyopathy. Survival analysis into regions of high risk (regions 90-129 and 130-180) and low risk (regions 1-89 and 200-288) was significant for sudden cardiac death (p = 0.011) and for heart failure death/transplant (p = 0.028). Our integrative genomic, structural, model from genotype to clinical data integration has implications for enhancing clinical genomics methodologies to improve risk stratification