an-innovative-method-endosome-isolation-from-mouse-heart-tissues-co

An Innovative Method of Endosome Isolation from Mouse Heart Tissues and Co-Culture with Cardiomyocytes

Endosomes are membrane-bound organelles playing essential roles in intracellular trafficking, signal transduction, and membrane recycling. Although their ...

University of Houston

The mechanisms regulating the cellular behaviour and cardiomyocyte organization during ventricular wall morphogenesis are poorly understood. Cardiomyocytes are surrounded by extracellular matrix (ECM) and interact with ECM via integrins. This study aims to determine whether and how β1 integrins regulate cardiomyocyte behaviour and organization during ventricular wall morphogenesis in the mouse.

β1 integrins regulate cellular behaviour and cardiomyocyte organization during ventricular wall formation.

Telomerase, by safeguarding damaged telomeres and bolstering DNA damage repair, has the capacity to heighten the radioresistance of tumour cells. Thus, in turn, can compromise the efficacy of radiotherapy (RT) and radioimmunotherapy. Our previous studies have revealed that the highly selective telomerase inhibitor, BIBR1532, possesses the potential to enhance the radiosensitivity of Non-small cell lung cancer (NSCLC). In this study, we delve further into the impact of BIBR1532 on the immune activation induced by RT and elucidate the underlying mechanisms.

BIBR1532 combined with radiotherapy induces ferroptosis in NSCLC cells and activates cGAS-STING pathway to promote anti-tumor immunity.

In the developing mammalian heart, the endocardium and the myocardium are separated by so-called cardiac jelly. Communication between the endocardium and the myocardium is essential for cardiac morphogenesis. How membrane-localized receptors and ligands achieve interaction across the cardiac jelly is not understood. Working in developing mouse cardiac morphogenesis models, we used a variety of cellular, imaging, and genetic approaches to elucidate this question. We found that myocardium and endocardium interacted directly through microstructures termed tunneling nanotube-like structures (TNTLs). TNTLs extended from cardiomyocytes (CMs) to contact endocardial cells (ECs) directly. TNTLs transported cytoplasmic proteins, transduced signals between CMs and ECs, and initiated myocardial growth toward the heart lumen to form ventricular trabeculae-like structures. Loss of TNTLs disturbed signaling interactions and, subsequently, ventricular patterning.

Tunneling nanotube-like structures regulate distant cellular interactions during heart formation.

Abnormalities of Ca2+ signaling in the heart lead to common cardiac remodeling in the pathogenesis of cardiovascular disorders. The activation of calmodulin-dependent protein kinase II (CaMKII) is regulated by elevated intracellular Ca2+ level in cardiomyocytes, driving the progression of myocardial dysfunction. In this study, using models of β2 adrenergic receptor (β2AR) deficiency in cardiomyocytes (β2AR-CKO), we observed an increased phosphorylation of CaMKII and upregulation of gene expression and protein level of the fibrotic marker connective tissue growth factor (CTGF) in the myocytes. In vivo treatment with the CaMKII inhibitor KN93 attenuated the upregulation of CTGF protein expression in β2AR-CKO hearts. Enhanced L-type calcium channel (LTCC) current was observed in β2AR-CKO cardiomyocytes following adrenergic stimulation, indicating a disruption of Ca2+ signaling. Treatment with the LTCC blocker nifedipine attenuated CaMKII activity and the expression of CTGF in β2AR-CKO hearts, confirming the upstream role of abnormal LTCC-Ca2+ signaling. Additionally, 8-month-old β2AR-CKO mice exhibited cardiac fibrosis and diastolic dysfunction. One month of in vivo nifedipine treatment improved both cardiac dysfunction and fibrosis in β2AR-CKO mice. These findings highlight the critical role of cardiomyocyte β2AR in maintaining LTCC-Ca2+ homeostasis. Loss of β2AR amplifies the Ca2+-CaMKII axis, promoting fibrosis and cardiomyopathy in aging hearts.

Cardiac β2 adrenergic receptor deletion drives calmodulin kinase II upregulation to induce connective tissue growth factor in cardiac fibrosis and diastolic dysfunction.

Article	Year
β1 integrins regulate cellular behaviour and cardiomyocyte organization during ventricular wall formation. Cardiovascular research\| PubMed ID: 38794925	2024
BIBR1532 combined with radiotherapy induces ferroptosis in NSCLC cells and activates cGAS-STING pathway to promote anti-tumor immunity. Journal of translational medicine\| PubMed ID: 38816831	2024
Tunneling nanotube-like structures regulate distant cellular interactions during heart formation. Science (New York, N.Y.)\| PubMed ID: 40080583	2025
Cardiac β2 adrenergic receptor deletion drives calmodulin kinase II upregulation to induce connective tissue growth factor in cardiac fibrosis and diastolic dysfunction. Function (Oxford, England)\| PubMed ID: 40796320	2025

Luqi Zhao

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