Commentary: Challenging paradigms Caldarone, Christopher A.
The Journal of thoracic and cardiovascular surgery,
June 2022, 2022-06-00, 20220601, Letnik:
163, Številka:
6
Journal Article
Commentary: In defense of the Hawthorne effect Caldarone, Christopher A.
The Journal of thoracic and cardiovascular surgery,
June 2021, 2021-06-00, 20210601, Letnik:
161, Številka:
6
Journal Article
Despite great progress in engineering functional tissues for organ repair, including the heart, an invasive surgical approach is still required for their implantation. Here, we designed an elastic ...and microfabricated scaffold using a biodegradable polymer (poly(octamethylene maleate (anhydride) citrate)) for functional tissue delivery via injection. The scaffold's shape memory was due to the microfabricated lattice design. Scaffolds and cardiac patches (1 cm × 1 cm) were delivered through an orifice as small as 1 mm, recovering their initial shape following injection without affecting cardiomyocyte viability and function. In a subcutaneous syngeneic rat model, injection of cardiac patches was equivalent to open surgery when comparing vascularization, macrophage recruitment and cell survival. The patches significantly improved cardiac function following myocardial infarction in a rat, compared with the untreated controls. Successful minimally invasive delivery of human cell-derived patches to the epicardium, aorta and liver in a large-animal (porcine) model was achieved.
Post-repair pulmonary venous obstruction is a common cause of reoperation after total anomalous pulmonary venous return repair. Herein, we report 3 cases of specific type of post-repair pulmonary ...venous obstruction with eccentric stenosis of pulmonary vein ostium due to retained composite neoseptum and the technique used for subsequent repair.
Hybrid palliation, the concept to stabilize univentricular circulation with bilateral pulmonary artery banding and maintenance of ductal patency, has significantly widened the therapeutic spectrum ...for patients with single-ventricle malformations or borderline hypoplasia. The concept has already been a part of early attempts to improve outcome in hypoplastic left heart syndrome but has not attracted much attention initially. Technical refinement and expertise have led to results that ultimately allowed the palliative strategy to gain traction and to be selectively adopted. By now, we have gained almost 2 decades of experience, and as much as hybrid palliation has changed our approach to single-ventricle management, new strategies and indications have been formed by this experience. We therefore review concepts and patterns of use of hybrid palliation as well as benefits and challenges of the respective pathways to highlight the current status of the hybrid procedure.
Pathological tissue remodelling by myofibroblast contraction is a hallmark of cardiac fibrosis. Myofibroblasts differentiate from cardiac fibroblasts under the action of transforming growth factor-β1 ...(TGF-β1), which is secreted into the extracellular matrix as a large latent complex. Integrin-mediated traction forces activate TGF-β1 by inducing a conformational change in the latent complex. The mesenchymal integrins αvβ5 and αvβ3 are expressed in the heart, but their role in the activation of TGF-β1 remains elusive. Here, we test whether targeting αvβ5 and αvβ3 integrins reduces latent TGF-β1 activation by cardiac fibroblasts with the goal to prevent the formation of α-smooth muscle actin (α-SMA)-expressing cardiac myofibroblasts and their contribution to fibrosis.
Using a porcine model of induced right ventricular fibrosis and pro-fibrotic culture conditions, we show that integrins αvβ5 and αvβ3 are up-regulated in myofibroblast-enriched fibrotic lesions and differentiated cultured human cardiac myofibroblasts. Both integrins autonomously contribute to latent TGF-β1 activation and myofibroblast differentiation, as demonstrated by function-blocking peptides and antibodies. Acute blocking of both integrins leads to significantly reduced TGF-β1 activation by cardiac fibroblast contraction and loss of α-SMA expression, which is restored by adding active TGF-β1. Manipulating integrin protein levels in overexpression and shRNA experiments reveals that both integrins can compensate for each other with respect to TGF-β1 activation and induction of α-SMA expression.
Integrins αvβ5 and αvβ3 both control myofibroblast differentiation by activating latent TGF-β1. Pharmacological targeting of mesenchymal integrins is a possible strategy to selectively block TGF-β1 activation by cardiac myofibroblasts and progression of fibrosis in the heart.
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