After myocardial infarction (MI), adult mammals exhibit scar formation, adverse left ventricular (LV) remodeling, LV stiffening, and impaired contractility, ultimately resulting in heart failure. Neonatal mammals, however, are capable of natural heart regeneration after MI. We hypothesized that neonatal cardiac regeneration conserves native biaxial LV mechanics after MI. Wistar rat neonates (1 day old, n = 46) and adults (8-10 weeks old, n = 20) underwent sham surgery or permanent left anterior descending coronary artery ligation. At 6 weeks after neonatal MI, Masson's trichrome staining revealed negligible fibrosis. Echocardiography for the neonatal MI (n = 15) and sham rats (n = 14) revealed no differences in LV wall thickness or chamber diameter, and both groups had normal ejection fraction (72.7% vs 77.5%, respectively, p = 0.1946). Biaxial tensile testing revealed similar stress-strain curves along both the circumferential and longitudinal axes across a full range of physiologic stresses and strains. The circumferential modulus (267.9 kPa vs 274.2 kPa, p = 0.7847), longitudinal modulus (269.3 kPa vs 277.1 kPa, p = 0.7435), and maximum shear stress (3.30 kPa vs 3.95 kPa, p = 0.5418) did not differ significantly between the neonatal MI and sham groups, respectively. In contrast, transmural scars were observed at 4 weeks after adult MI. Adult MI hearts (n = 7) exhibited profound LV wall thinning (p < 0.0001), chamber dilation (p = 0.0246), and LV dysfunction (ejection fraction 45.4% vs 79.7%, p < 0.0001) compared to adult sham hearts (n = 7). Adult MI hearts were significantly stiffer than adult sham hearts in both the circumferential (321.5 kPa vs 180.0 kPa, p = 0.0111) and longitudinal axes (315.4 kPa vs 172.3 kPa, p = 0.0173), and also exhibited greater maximum shear stress (14.87 kPa vs 3.23 kPa, p = 0.0162). Our study is the first to show that native biaxial LV mechanics are conserved after neonatal heart regeneration following MI, thus adding biomechanical support for the therapeutic potential of cardiac regeneration in the treatment of ischemic heart disease.
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http://dx.doi.org/10.1016/j.jmbbm.2022.105074 | DOI Listing |
Nat Cardiovasc Res
January 2025
Department of Pharmacy at the Second Affiliated Hospital, and Department of Pharmacology at College of Pharmacy (The Key Laboratory of Cardiovascular Research, Ministry of Education; National Key Laboratory of Frigid Zone Cardiovascular Diseases), Harbin Medical University, Harbin, China.
Targeting the cardiomyocyte cell cycle is a promising strategy for heart repair following injury. Here, we identify a cardiac-regeneration-associated PIWI-interacting RNA (CRAPIR) as a regulator of cardiomyocyte proliferation. Genetic ablation or antagomir-mediated knockdown of CRAPIR in mice impairs cardiomyocyte proliferation and reduces heart regenerative potential.
View Article and Find Full Text PDFArch Dis Child
January 2025
Department of Child Life and Health, University of Edinburgh Institute for Regeneration and Repair, Edinburgh, UK.
Objective: To obtain priority consensus for outcome measures of oral corticosteroid treatment of preschool wheeze that represent stakeholder groups.
Design: (1) A systematic review to identify a set of outcome measures; (2) an international survey for healthcare professionals (HCPs) and a nominal group meeting with parents; (3) a final consensus nominal group meeting with key HCPs (trial investigators and paediatric emergency medicine clinicians) and the same parent group.
Main Outcome Measures: Consensus priority of treatment outcome measures, outcome minimal clinically important differences (MCIDs) and level of concerns about adverse effects.
Nat Cardiovasc Res
January 2025
School of Cardiovascular and Metabolic Medicine & Sciences, British Heart Foundation Centre of Research Excellence, James Black Centre, King's College London, London, UK.
Int J Biol Macromol
January 2025
Polymers and Pigments Department, Chemical Industries Research Institute, National Research Centre, Dokki, Giza 12622, Egypt.
Integrating nanotechnology with tissue engineering has revolutionized biomedical sciences, enabling the development of advanced therapeutic strategies. Tissue engineering applications widely utilize alginate due to its biocompatibility, mild gelation conditions, and ease of modification. Combining different nanomaterials with alginate matrices enhances the resulting nanocomposites' physicochemical properties, such as mechanical, electrical, and biological properties, as well as their surface area-to-volume ratio, offering significant potential for tissue engineering applications.
View Article and Find Full Text PDFThe intricate development and functionality of the mammalian heart are influenced by the heterogeneous nature of cardiomyocytes (CMs). In this study, single-cell and spatial transcriptomics were utilized to analyze cells from neonatal mouse hearts, resulting in a comprehensive atlas delineating the transcriptional profiles of distinct CM subsets. A continuum of maturation states was elucidated, emphasizing a progressive developmental trajectory rather than discrete stages.
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