Kardiovaskulära sjukdomar är fortfarande en av de främsta dödsorsakerna i dag. Den främsta orsaken till sjukdomen är skador på hjärtcellerna, som kanske inte kan repareras av sig själva, så att utveckla en ny terapi för att regenerera eller reparera hjärtcellerna är ett viktigt mål inom forskningen om hjärtsjukdomar. Tidigare forskning har visat att vissa kardiogena parakrina faktorer som tillväxtfaktorer eller utsöndrade proteiner kan påverka hjärtats utveckling och regenerering. I den här studien valdes en av de parakrina faktorerna, placentaväxtfaktor (PLGF), ut för att verifiera dess inflytande på kardiomyogenes och vaskulogenes genom in vivo- och in vitro-experiment. Genom in vivo-experiment injicerades humana embryonala stamceller (hESC) som innehöll kemiskt modifierat PLGF mRNA i njurkapselskiktet hos musen, och en månad senare samlades njurarna in och färgades genom sektionering för att bestämma differentieringen av hESC. Genom in vitro-experiment inducerades hESC som avlägsnats PLGF-genen genom CRISPR-Cas9 till tre olika celler (kardiomyocyter, glatta muskelceller och endotelceller) enligt ett etablerat protokoll, och sedan analyserades cellerna med fluorescensaktiverad cellsortering (FACS) för att bestämma differentieringsnivån. Enligt experimenten krävs PLGF för induktion av kärlceller in vitro (endotelceller och glatta muskelceller) och skapandet av in vivo-kärl som genererats från hESCs, och det kan också påverka induktionen av kardiomyocyter i viss utsträckning, vilket krävde ytterligare forskning. Denna studie ger information om PLGF:s kritiska funktioner i kardiomyogenes och vaskulogenes, vilket kan bana väg för utvecklingen av nya terapier för regenerering av hjärtat. / Cardiovascular disease is still a leading cause of mortality nowadays. The main cause of the disease is the damage to heart cells, which may not be repaired by itself so developing a new therapy to regenerate or repair the heart cells is a major goal in cardiac disease research. Through previous research, some cardiogenic paracrine factors like growth factors or secreted proteins may influence heart development and regeneration. In this study, one of the paracrine factors, the placental growth factor (PLGF), was selected to verify its influence on cardiomyogenesis and vasculogenesis through in vivo and in vitro experiments. Through in vivo experiments, human embryonic stem cells(hESCs) containing PLGF mRNA which was modified chemically were injected into the mouse kidney capsule layer, and one month later the kidneys were collected and stained by sectioning to determine the differentiation of hESCs. Through in vitro experiments, hESC which were removed PLGF gene by CRISPR-Cas9 were induced into three different cells (cardiomyocyte, smooth muscle cell, and endothelial cell) followed an established protocol, and then the cells were analyzed by fluorescence-activated cell sorting (FACS) to determine the differentiation level. According to experiments, PLGF is required for the induction of in vitro vascular cells (endothelial cell and smooth muscle cell) and the creation of in vivo vasculature generated from hESCs, and it may also influence cardiomyocyte induction to some extent which needed further research. This study offers information on the critical functions of PLGF in cardiomyogenesis and vasculogenesis, potentially paving the way for the development of new heart regeneration therapies.

Short summary: Background: High cardiovascular risk in patients with chronic kidney disease is partly due to mineral dysbalance, microinflammation and oxidative stress. CKD patients accumulate traditional and non-traditional CV risk factors. FGF23, MMPs and PlGF belong among these non-traditional biomarkers of CV risk. FGF23 is a phosphaturic hormone and inhibitor of calcitriol synthesis. It is associated with vascular calcifications. Matrix-metalloproteinases (e.g. MMP-2, MMP-9) are proteolytic, proinflammatory enzymes, contributing to myocardial remodelation. Placental growth factor (PlGF) is a proangiogenic cytokine that is associated with LV hypertrophy in animal model. Plasmatic FGF23, MMPs and PlGF are elevated in CKD. Aim: We aimed to describe dynamic changes between several novel biomarkers of CV risk (FGF23, MMP-2, MMP-9 and PlGF) in CKD stages 1-5, to describe their mutual correlations and possible association with traditional CV risk markers. We studied possible association of laboratory and echocardiographic parameters in patients with CKD stages 2-4. Methods: In a cross-sectional study we evaluated 80 patiens with CKD 1-5 and 44 healthy controls. In a prospective study we evaluated echocardiographic and laboratory parameters in 62 patients with CKD 2-4 for an average study period of 36±10...

Short summary: Background: High cardiovascular risk in patients with chronic kidney disease is partly due to mineral dysbalance, microinflammation and oxidative stress. CKD patients accumulate traditional and non-traditional CV risk factors. FGF23, MMPs and PlGF belong among these non-traditional biomarkers of CV risk. FGF23 is a phosphaturic hormone and inhibitor of calcitriol synthesis. It is associated with vascular calcifications. Matrix-metalloproteinases (e.g. MMP-2, MMP-9) are proteolytic, proinflammatory enzymes, contributing to myocardial remodelation. Placental growth factor (PlGF) is a proangiogenic cytokine that is associated with LV hypertrophy in animal model. Plasmatic FGF23, MMPs and PlGF are elevated in CKD. Aim: We aimed to describe dynamic changes between several novel biomarkers of CV risk (FGF23, MMP-2, MMP-9 and PlGF) in CKD stages 1-5, to describe their mutual correlations and possible association with traditional CV risk markers. We studied possible association of laboratory and echocardiographic parameters in patients with CKD stages 2-4. Methods: In a cross-sectional study we evaluated 80 patiens with CKD 1-5 and 44 healthy controls. In a prospective study we evaluated echocardiographic and laboratory parameters in 62 patients with CKD 2-4 for an average study period of 36±10...