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Vascular endothelial growth factor B interferes with angiogenesis and the electrical functions of the heart

  • Health and well-being

The doctoral thesis of Olli-Pekka Hätinen, MSc, provides crucial information about one potential gene therapy candidate for cardiac diseases, VEGF-B, and highlights issues that must be taken into consideration when developing new therapies. It also introduced a step-by-step method for the isolation of endothelial cells from the porcine heart that offers new possibilities in the emerging fields of genomics, transcriptomics, cell and tissue studies in cardiovascular medicine and vascular biology.

Cardiovascular diseases are responsible for over one-third of all deaths in developed countries. Most of the patients recover from the primary complications of myocardial infarction, but later develop secondary complications, such as arrhythmias or ischemic cardiomyopathy can cause the death of every second survivor.

Vascular endothelial growth factors (VEGFs) are considered as potentially interesting candidates for novel therapeutic approaches. One of the VEGFs, VEGF-B, has been shown to induce myocardium specific angiogenesis; however, the mechanism behind this finding is far from clear.

VEGF-B increases susceptibility to arrhythmias

In the first study, the researchers concentrated on the arrhythmic effect of VEGF-B and on understanding the molecular mechanisms behind the lethal arrhythmia occurring after a myocardial infarction. They found that overexpressing VEGF-B increased the susceptibility to cardiac arrhythmias and sympathetic nerve sprouting.

Primary endothelial cells play a crucial role in cardiovascular research

Pigs are the most frequently used large animals in cardiovascular studies; however, there is no rapid and convenient protocol for the isolation of endothelial cells from pig heart. Previously used methods are time-consuming, causing a change in both the transcription properties and phenotype of the endothelial cells, thus potentially changing tissue-specific properties. A fast isolation protocol was developed that helps to retain these specific properties.

Regulation of nicotine acetylcholine receptors has a role in VEGF-B induced angiogenesis

The third study examined the myocardium specific effect of VEGF-B. It was hypothesized that VEGF-B would induce angiogenesis via the regulation of nicotine acetylcholine receptors (nAChRs). Various experiments revealed that the regulation of nAChRs plays a vital role in myocardium-specific angiogenesis.

The doctoral dissertation of Olli-Pekka Hätinen, Master of Science, entitled Vascular endothelial growth factor B interferes with angiogenesis and the electrical functions of the heart, will be examined at the Faculty of Health Sciences. The Opponent in the public examination will be Professor Heikki Ruskoaho of the University of Helsinki, and the Custos will be Academy Professor Seppo Ylä-Herttuala of the University of Eastern Finland. The public examination  will be held in Finnish at Kuopio Campus, Medistudia Auditorium MS302, on 13 June 2020 starting at 12 noon.

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Hätinen, Olli-Pekka. Vascular endothelial growth factor B interferes with angiogenesis and the electrical functions of the heart: pre-clinical studies of intramyocardial gene therapy