Browsing by Subject "Cardiovascular biology"

Now showing 1 - 3 of 3
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    Dbh+ catecholaminergic cardiomyocytes contribute to the structure and function of the cardiac conduction system in murine heart
    (Springer Nature, 2023-11-28) Sun, Tianyi; Grassam-Rowe, Alexander; Pu, Zhaoli; Li, Yangpeng; Ren, Huiying; An, Yanru; Guo, Xinyu; Hu, Wei; Liu, Ying; Zheng, Yuqing; Liu, Zhu; Kou, Kun; Ou, Xianhong; Chen, Tangting; Fan, Xuehui; Liu, Yangyang; Tu, Shu; He, Yu; Ren, Yue; Chen, Ao; Shang, Zhouchun; Xia, Zhidao; Miquerol, Lucile; Smart, Nicola; Zhang, Henggui; Tan, Xiaoqiu; Shou, Weinian; Lei, Ming; Pediatrics, School of Medicine
    The heterogeneity of functional cardiomyocytes arises during heart development, which is essential to the complex and highly coordinated cardiac physiological function. Yet the biological and physiological identities and the origin of the specialized cardiomyocyte populations have not been fully comprehended. Here we report a previously unrecognised population of cardiomyocytes expressing Dbhgene encoding dopamine beta-hydroxylase in murine heart. We determined how these myocytes are distributed across the heart by utilising advanced single-cell and spatial transcriptomic analyses, genetic fate mapping and molecular imaging with computational reconstruction. We demonstrated that they form the key functional components of the cardiac conduction system by using optogenetic electrophysiology and conditional cardiomyocyte Dbh gene deletion models. We revealed their close relationship with sympathetic innervation during cardiac conduction system formation. Our study thus provides new insights into the development and heterogeneity of the mammalian cardiac conduction system by revealing a new cardiomyocyte population with potential catecholaminergic endocrine function.
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    Experimental and theoretical model of microvascular network remodeling and blood flow redistribution following minimally invasive microvessel laser ablation
    (Springer Nature, 2024-04-16) Gruionu, Gabriel; Baish, James; McMahon, Sean; Blauvelt, David; Gruionu, Lucian G.; Lenco, Mara Onita; Vakoc, Benjamin J.; Padera, Timothy P.; Munn, Lance L.; Medicine, School of Medicine
    Overly dense microvascular networks are treated by selective reduction of vascular elements. Inappropriate manipulation of microvessels could result in loss of host tissue function or a worsening of the clinical problem. Here, experimental, and computational models were developed to induce blood flow changes via selective artery and vein laser ablation and study the compensatory collateral flow redistribution and vessel diameter remodeling. The microvasculature was imaged non-invasively by bright-field and multi-photon laser microscopy, and optical coherence tomography pre-ablation and up to 30 days post-ablation. A theoretical model of network remodeling was developed to compute blood flow and intravascular pressure and identify vessels most susceptible to changes in flow direction. The skin microvascular remodeling patterns were consistent among the five specimens studied. Significant remodeling occurred at various time points, beginning as early as days 1–3 and continuing beyond day 20. The remodeling patterns included collateral development, venous and arterial reopening, and both outward and inward remodeling, with variations in the time frames for each mouse. In a representative specimen, immediately post-ablation, the average artery and vein diameters increased by 14% and 23%, respectively. At day 20 post-ablation, the maximum increases in arterial and venous diameters were 2.5× and 3.3×, respectively. By day 30, the average artery diameter remained 11% increased whereas the vein diameters returned to near pre-ablation values. Some arteries regenerated across the ablation sites via endothelial cell migration, while veins either reconnected or rerouted flow around the ablation site, likely depending on local pressure driving forces. In the intact network, the theoretical model predicts that the vessels that act as collaterals after flow disruption are those most sensitive to distant changes in pressure. The model results correlate with the post-ablation microvascular remodeling patterns.
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    Female and male mice have differential longterm cardiorenal outcomes following a matched degree of ischemia–reperfusion acute kidney injury
    (Springer Nature, 2022-01-12) Soranno, Danielle E.; Baker, Peter, II.; Kirkbride-Romeo, Lara; Wennersten, Sara A.; Ding, Kathy; Keith, Brysen; Cavasin, Maria A.; Altmann, Christopher; Bagchi, Rushita A.; Haefner, Korey R.; Montford, John; Gist, Katja M.; Vergnes, Laurent; Reue, Karen; He, Zhibin; Elajaili, Hanan; Okamura, Kayo; Nozik, Eva; McKinsey, Timothy A.; Faubel, Sarah; Pediatrics, School of Medicine
    Acute kidney injury (AKI) is common in patients, causes systemic sequelae, and predisposes patients to long-term cardiovascular disease. To date, studies of the effects of AKI on cardiovascular outcomes have only been performed in male mice. We recently demonstrated that male mice developed diastolic dysfunction, hypertension and reduced cardiac ATP levels versus sham 1 year after AKI. The effects of female sex on long-term cardiac outcomes after AKI are unknown. Therefore, we examined the 1-year cardiorenal outcomes following a single episode of bilateral renal ischemia–reperfusion injury in female C57BL/6 mice using a model with similar severity of AKI and performed concomitantly to recently published male cohorts. To match the severity of AKI between male and female mice, females received 34 min of ischemia time compared to 25 min in males. Serial renal function, echocardiograms and blood pressure assessments were performed throughout the 1-year study. Renal histology, and cardiac and plasma metabolomics and mitochondrial function in the heart and kidney were evaluated at 1 year. Measured glomerular filtration rates (GFR) were similar between male and female mice throughout the 1-year study period. One year after AKI, female mice had preserved diastolic function, normal blood pressure, and preserved levels of cardiac ATP. Compared to males, females demonstrated pathway enrichment in arginine metabolism and amino acid related energy production in both the heart and plasma, and glutathione in the plasma. Cardiac mitochondrial respiration in Complex I of the electron transport chain demonstrated improved mitochondrial function in females compared to males, regardless of AKI or sham. This is the first study to examine the long-term cardiac effects of AKI on female mice and indicate that there are important sex-related cardiorenal differences. The role of female sex in cardiovascular outcomes after AKI merits further investigation.