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Biomedical subjects

David Crossman

Publications and source records attributed to David Crossman.

4 recordsLinked to original sources
PubMed2006

Interleukin-1beta and signaling of interleukin-1 in vascular wall and circulating cells modulates the extent of neointima formation in mice.

Interleukin (IL)-1 is an important mediator of inflammation and cardiovascular disease. Here, we examined the role of IL-1 in arterial neointima formation. Carotid artery neointima was induced by ligation, and arteries were harvested 4 weeks after injury. The neointima/media of mice deficient in the IL-1 signaling receptor (IL-1R1(-/-)) was significantly reduced compared to IL-1R1(+/+) controls (P < 0.01). IL-1R1(+/+) mice receiving subcutaneous IL-1ra also had significantly reduced neointima/media compared with placebo (P < 0.05). IL-1beta(-/-) mice had reduced neointima/media compared to wild-type (P < 0.05), whereas IL-1alpha(-/-) mice were no different from controls. Mice deficient in the P2X(7) receptor (involved in IL-1 release) or caspase-1 (involved in IL-1 activation) did not differ in their response to carotid ligation compared to controls. To examine the site of IL-1 signaling, we generated chimeric mice. IL-1R1(+/+) mice receiving IL-1R1(-/-) marrow and IL-1R1(-/-) mice receiving IL-1R1(+/+) marrow both had significantly reduced neointima/media compared with IL-1R1(+/+) to IL-1R1(+/+) (P < 0.05) but had significantly greater neointima/media than IL-1R1(-/-) to IL-1R1(-/-) controls (P < 0.05). These data confirm the importance of IL-1beta signaling in mediating arterial neointima formation and suggest the involvement of IL-1 signaling in both circulating and arterial wall cells. Furthermore, receptor antagonism may be a better therapeutic target than interruption of IL-1beta processing or release.

Animals↗
PubMed2005

Differential gene expression in coronary arteries from patients presenting with ischemic heart disease: further evidence for the inflammatory basis of atherosclerosis.

BACKGROUND AND OBJECTIVE: The pathogenesis of human coronary artery disease (CAD) is likely to require the transcription of many different genes. We report here the differential gene expression profiling of human CAD using copy DNA (cDNA)/nylon array hybridization techniques. METHODS AND RESULTS: Human coronary arteries were obtained at the time of cardiac transplantation. Ten patients were transplanted for ischemic heart disease (IHD) and 5 for dilated cardiomyopathy (DCM). We generated a customized cDNA array containing 9206 clones and after hybridization of patient samples, data reduction, and refinement, identified 515 sequence-verified, differentially expressed clones. These clones represented 361 genes that were differentially expressed at significant levels between IHD and DCM arteries (t test, P < .05). Of these clones, 70% were defined genes of known function and 30% were genes of unknown function. Of the differentially expressed genes, 53.6% were up-regulated and 46.4% were down-regulated. Hierarchical clustering was performed and several distinct functional clusters were identified, including a cluster of genes related to inflammatory mechanisms. Validation by real-time polymerase chain reaction was undertaken with 2 genes known to be up-regulated in atherosclerosis (interleukin 1beta [IL-1beta] and IL-8) and 2 novel genes identified by the array analysis (signal transducer and activator of transcription 6 [STAT6] and IL-1 receptor-associated kinase [IRAK]). Differential expression of IL-1beta, IL-8, and STAT6 were confirmed by this method. Immunohistochemistry of STAT6 demonstrated increased expression in vascular smooth muscle cells of IHD coronary arteries. CONCLUSION: These data support the inflammatory basis of human atherosclerotic CAD and identify novel genes in atherosclerosis.

Cluster Analysis↗
PubMed2004

The influence of physical stent parameters upon restenosis.

In this paper we examine whether the structure, geometry and dimensions of coronary stents influence the occurrence of restenosis. Whilst many consider these parameters to be less important since the advent of drug-eluting stents, this view reveals a poor appreciation of the technological development of stents over the last 18 years. Early 'slotted tube' stents were completely inflexible and posed major problems for delivery; and early 'coil' stents had poor radial strength, allowing considerable tissue prolapse. Nowadays, we are used to greatly improved physical stent parameters, which provide better deliverability, visibility, procedural success and scaffolding performance. Many of these physical parameters also impact upon restenosis, even in the current era of drug-eluting stent. In this paper we examine the contribution of mode of expansion (self vs. balloon-expandable), design (coil vs. tube), length and width to restenosis. We also consider the more subtle influence of advanced slotted tube vs. modular design, percent metal coverage, strut thickness, strut shape, surface smoothness and alloy composition.

Angioplasty, Balloon, Coronary↗