The heart pumps blood through the vascular system, supplying the cells with oxygen and energy. The smooth muscle cells in the vessels finely regulate blood flow. If they cannot do their job, malformations and dilations of the vascular system can occur, according to a research team led by Professor Alfred Nordheim of the Interfaculty Institute for Cell Biology at the University of Tübingen, together with scientists from Tübingen , Münster and Uppsala. sweden Their new study, the result of experiments in an animal model, could be applied experimentally to a model of a specific disease of the retina of the eye in premature babies, as it points to a potential new approach to treatment. The study has been published in Circulation Research.
In arterial and venous blood vessels, smooth muscle cells selectively contract and relax to regulate where more and less blood flows. They also give the vascular network the strength it needs to support blood pressure. In one experiment, Alfred Nordheim and his team inactivated the serum response factor (SRF) gene in mice, which significantly regulates the ability of cells to contract. “This caused significant vasodilation and vascular malformations in the blood vessels,” Nordheim reported.
Reduced blood flow
The malformations involve direct connections between arteries and veins, Nordheimer explained. “Arteries take a shortcut to veins, passing through tiny microvessels. Similar malformations are also known in certain rare blood vessel diseases in humans. Our team was able to show that these shortcuts cause the surrounding tissue to receive reduced blood flow.” . The lack of strength in the smooth muscle cells sometimes even led to ruptures in the vessels, Nordheim said.
Aside to another disease
This newly acquired knowledge also put us on the path to a completely different disease called ischemic retinopathy. This is a disease of the retina in premature babies, which in the worst case can lead to blindness.”
Dr. Michael Orlich, lead author of the study, Uppsala University
An excessive reaction in the growth of blood vessels leads to pathological changes in cells known as pericytes. “Among other things, pathological pericytes produce contractile proteins, similar to smooth muscle cells,” explains Orlich.
“We had expected that serum response factor also plays an important role here. Furthermore, we hypothesized that the symptoms of retinal disease would improve if pericyte overreaction was reduced.”
The research team tested their assumptions experimentally in mice in which a disease comparable to ischemic retinopathy had been induced. “When we specifically disabled the serum response factor in the pericytes of these mice, the symptoms decreased,” Orlich said, summarizing the results. This, he says, could be a potential approach to new treatments for ischemic retinopathies in humans.
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Journal reference:
Orlich, MM, et al. (2022) Mural cell SRF controls pericyte migration, vessel patterning, and blood flow. Research in Circulation. doi.org/10.1161/CIRCRESAHA.122.321109.