Expression of mRNA for molecules that regulate angiogenesis, endothelial cell survival, and vascular permeability is altered in endothelial cells isolated from db/db mouse hearts

• Published in: Histochemistry and cell biology 2024-12, Vol.162 (6), p.523-539
• Main Authors: Bartkowiak, Krzysztof, Bartkowiak, Mateusz, Jankowska-Steifer, Ewa, Ratajska, Anna, Czarnowska, Elżbieta, Kujawa, Marek, Aniołek, Olga, Niderla-Bielińska, Justyna
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Aorta; Biochemistry; Biomedical and Life Sciences; Biomedicine; Capillary Permeability; Cardiovascular diseases; Cell Biology; Cell Survival; Cells, Cultured; Confocal microscopy; Developmental Biology; Endothelial cells; Endothelial Cells - metabolism; Gene expression; Heart; Hyperglycemia; Male; Metabolic syndrome; Mice; Mice, Inbred C57BL; Microscopy; Microvasculature; mRNA; Myocardium; Myocardium - metabolism; Myocardium - pathology; Neovascularization, Physiologic; Original Paper; Permeability; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Transmission electron microscopy; Ultrastructure; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Vascular endothelial growth factor receptors; Vascular permeability factor
• ISSN: 0948-6143; 1432-119X; 1432-119X
• DOI: 10.1007/s00418-024-02327-4

Metabolic syndrome (MetS) is a condition that includes symptoms, such as obesity, hyperglycemia, and hypertension, which elevate cardiovascular risk. An impaired angiogenic response of endothelial cells (ECs) in heart and peripheral organs has been proposed in MetS, but the mechanisms of this phenomenon have not been thoroughly explored. Results obtained from evaluating the whole myocardium are inconsistent, since different types of cells react differently to MetS environment and a variety of molecular pathways are involved in the angiogenic response. Therefore, the aim of this paper was to study one selected pathway—the VEGF/VEGFR pathway, which regulates the angiogenic response and microvascular permeability in ECs isolated from db/db mouse hearts. The expression of mRNAs for VEGF/VEGFR axis proteins was assessed with RT-PCR in ECs isolated from control and db/db mouse myocardium. The density of CD31-, VEGFR2-, and VE-cadherin-positive cells was examined with confocal microscopy, and the ultrastructure of ECs was analyzed with transmission electron microscopy. The aortic ring assay was used to assess the capacity of ECs to respond to angiogenic stimuli. Our results showed a decreased number of microvessels, diminished expression of VE-cadherin and VEGFR2 and widened gaps between the ECs of microcapillaries. The aortic ring assay showed a diminished number of sprouts in db/db mice. These results may indicate that ECs in MetS enhance the production of mRNA for VEGF/VRGFR axis proteins, yet sprout formation and vascular barrier maintenance are limited. These novel data may provide a foundation for further studies on ECs dysfunction in MetS.