The lymphatic vasculature has an essential role in maintaining normal fluid balance in tissues and modulating the inflammatory response to injury or pathogens, thus, disruption of normal development or the function of lymphatic vessels can have severe consequences. In the heart, reduced lymphatic function can lead to myocardial oedema and persistent inflammation. The soluble epoxide hydrolase (sEH) is an enzyme that metabolizes epoxides of polyunsaturated fatty acids (PUFAs) into diols and is upregulated in metabolic diseases (including diabetes). An increase in sEH expression and activity has been directly implicated in diabetes-associated comorbidities e.g. heart failure and retinopathy. Single nuclei RNA-sequencing data from the hearts of diabetic and non-diabetic mice that express or lacking the sEH in cardiomyocytes, revealed that sEH-deletion results in reduced lymphangiogenesis at the same time as increasing blood endothelial cell numbers (unpublished).

To study this in more detail, mice have been generated that either lack the sEH only in lymphatic endothelial cells or overexpress the enzyme in lymphatic and blood endothelial cells.

The GREP project will be based around the phenotyping of these animals, and involves using confocal and light sheet microscopy to study lymphatic vessels in the heart (lymphatic network, vessel diameter, branching points and smooth muscle cell coverage). Work will also involve SDS-PAGE, in vitro assays using cultured endothelial cells and the isolation of samples to measure levels of PUFA epoxides and diols.