Abstract This paper will forecast advancements in coronary revascularization by 2040, drawing on historical trends and recent breakthroughs. Having forecasted in 2000 the impact of innovations like drug-eluting stents, coronary computed tomography angiography, and bioresorbable scaffolds, the authors examine the evolving landscape of coronary artery disease treatment emphasizing artificial intelligence and omics sciences. Imagenomics—the integration of imaging and omics—will be a transformative tool with artificial intelligence enabling more personalized decisions between pharmacological and mechanical revascularization. The shift towards minimally invasive, image-guided procedures is discussed along with the potential obsolescence of current antiplatelet and anticoagulant therapies with novel biomimetic peptides like CD31-covalently bound to metallic or polymeric devices. Advances in photon-counting computed tomography and Fibre Optic Real Shape promise high-resolution imaging with lower radiation, enhancing procedural safety and diagnostic accuracy. It is anticipated that robotics and 3D holograms in percutaneous and surgical revascularization will improve precision and the resulting outcomes. Additionally, the need for mechanical revascularization for younger patients may decline due to effective plaque regression therapies and novel potent anti-atherogenic biologics. However, the aging population will drive demand for mechanical interventions, with advancements in atherectomy and lithotripsy techniques improving outcomes in complex, calcified lesions. This comprehensive analysis outlines a future where myocardial revascularization becomes increasingly personalized, with technology-driven interventions redefining cardiovascular medicine.
Summary Interleukin‐5 (IL‐5) is a T helper type 2 cytokine, which is implicated in the pathogenesis of eosinophilic diseases such as asthma. Both peripheral blood mononuclear cells (PBMC) and primary human T cells display similar patterns of IL‐5 expression when stimulated with both phorbol‐12‐myristate 13‐acetate and phytohaemagglutinin. The expression of IL‐5 stimulated by these agents was shown to require de novo transcription and translation. However, although dexamethasone was a potent inhibitor of both IL‐5 release and messenger RNA accumulation from PBMC and T cells, dexamethasone had no effect on the luciferase activity of a reporter construct under the control of an IL‐5 promoter region transiently transfected into primary human T cells. Furthermore, dexamethasone appeared to decrease the stability of IL‐5 messenger RNA and this effect was dependent upon de novo transcription. Taken together, the results presented here suggest that, whilst transcriptional processes predominantly regulate IL‐5 release, the mechanism by which dexamethasone inhibits IL‐5 is post‐transcriptional.
It has been suggested that there is a preferential coupling in heart muscle between the inhibitory G protein (G i ) and the β 2 -subtype of the β-adrenergic receptor (β-AR), since pertussis toxin (which inactivates G i ) reveals latent β 2 -ARs in rat and mouse myocytes. We have previously shown that guinea pigs treated with norepinephrine (NE) for 7 days have myocytes that are desensitized to β-AR-agonist stimulation, and that pertussis toxin restores these responses. The purpose of the present investigation was to determine whether pertussis toxin specifically upregulated β 2 -ARs in myocytes from NE-treated guinea pigs. The sole β-AR subtype in control guinea pig myocytes was confirmed as β 1 -AR by radioligand binding, single-cell autoradiography, and concentration-response curves to isoproterenol in contracting myocytes. In contrast, a minor pool of β 2 -ARs was observed in rat myocytes by use of the same methods. NE treatment decreased the maximum isoproterenol response (relative to high Ca 2+ ) from 0.89 ± 0.06 to 0.58 ± 0.08 ( n = 7, P < 0.01) and the pD 2 (−log EC 50 ) from 8.8 ± 0.2 to 7.5 ± 0.2 ( n = 7, P < 0.01). Pertussis toxin treatment increased the isoproterenol-to-Ca 2+ ratio to 0.88 ± 0.04 ( n = 6, P < 0.05) and the pD 2 to 8.6 ± 0.3 ( P < 0.01). This was not mediated by increases in either number or function of β 2 -ARs. G i is therefore able to modulate β 1 -AR responses in guinea pig myocytes.
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