Isa Lindgren

Chiesi Pharma AB · Preclinical

Fetal cardiomyocytes shift from glycolysis to oxidative phosphorylation around the time of birth. Myeloid ecotropic viral integration site 1 (MEIS1) is a transcription factor that promotes glycolysis in hematopoietic stem cells. We reasoned that MEIS1 could have a similar role in the developing heart. We hypothesized that suppression of MEIS1 expre...

Key points: Plasma thyroid hormone (tri-iodo-l-thyronine; T3 ) concentrations rise near the end of gestation and is known to inhibit proliferation and stimulate maturation of cardiomyocytes before birth. Thyroid hormone receptors are required for the action of thyroid hormone in fetal cardiomyocytes. Loss of thyroid hormone receptor (TR)α1 abolish...

Objective: Prenatal hypertension leads to mitral annular dilation and is linked to changes in valvular extracellular matrix (ECM) and cell cycle genes including TGFβ-1, BMPs and FGF. We hypothesized that these changes are exacerbated by additional mechanical stress. Methods: Fetal sheep received 8 days of plasma infusion to induce hypertension (HTN...

Some biomechanical studies from fossil specimens suggest that sustained flapping flight of birds could have appeared in their Mesozoic ancestors. We challenge this idea because a suitable musculoskeletal anatomy is not the only requirement for sustained flapping flight. We propose the “heart to fly” hypothesis that states that sustained flapping fl...

Sexual dimorphism depends on sex-biased gene expression, but the contributions of microRNAs (miRNAs) have not been globally assessed. We therefore produced an extensive small RNA sequencing data set to analyze male and female miRNA expression profiles in mouse, opossum, and chicken. Our analyses uncovered numerous cases of somatic sex-biased miRNA...

Fetal growth restriction programs an increased risk of cardiovascular disease in adulthood but the actual mechanisms of this developmental programming are not fully understood. Previous studies in mammalian models suggest that hearts of growth-restricted fetuses have reduced cardiomyocyte number due to reduced proliferation and premature cardiomyoc...

Unlabelled: The β-adrenergic response is impaired in failing hearts. When studying β-adrenergic function in vitro, the half-maximal effective concentration (EC50 ) is an important measure of ligand response. We previously measured the in vitro contraction force response of chicken heart tissue to increasing concentrations of adrenaline, and observ...

Fetal cardiac growth in mammalian models occurs primarily by cell proliferation (hyperplasia). However, most cardiomyocytes lose the ability to proliferate close to term and heart growth continues by increasing cell size (hypertrophy). In mammals, the thyroid hormone triiodothyronine (T3) is an important driver of this process. Chicken cardiomyocyt...

Analysis of selective sweeps to pinpoint causative genomic regions involved in chicken domestication has revealed a strong selective sweep on chromosome 4 in layer chickens. The autoregulatory α-adrenergic receptor 2C (ADRA2C) gene is the closest to the selective sweep and was proposed as an important gene in the domestication of layer chickens. Th...

Prenatal hypoxia leads to an increased risk of adult cardiovascular disease. We have previously demonstrated a programming effect of prenatal hypoxia on the cardiac beta-adrenergic (βAR) response. The aim of this study was to determine 1) if the decrease in βAR sensitivity in prenatally hypoxic 5 week chicken hearts is linked to changes in β1AR/β2A...

Experiments investigated maturation of endothelial function in the postnatal period (P). Carotid arteries isolated from newborn (P day 1, P1) to P21 mice were assessed in myographs at transmural pressure (PTM) of 20mmHg (P1 blood pressure, BP). Acetylcholine was ineffective in P1 but powerfully dilated P7 arteries, whereas NO-donor DEA-NONOate caus...

Prolonged fetal hypoxia leads to growth restriction and can cause detrimental prenatal and postnatal alterations. The embryonic chicken is a valuable model to study the effects of prenatal hypoxia, but little is known about its long-term effects on cardiovascular regulation. We hypothesized that chicken embryos incubated under chronic hypoxia would...

Genetic selection programs have imposed large phenotypic changes in domesticated chicken breeds that are also apparent during embryonic development. Broilers, for example, have a faster growth rate before hatching in comparison with White Leghorns, indicating that the allocation of resources toward different functions already begins before hatching...

The reactivity of human fetoplacental arteries is regulated by humoral and local factors of maternal and fetal origin. The chorioallantoic (CA) arteries of bird embryos are homologous to fetoplacental arteries and fulfill the same gas-exchange purpose without maternal influences, but their reactivity has not been studied in detail. In the present s...

Prenatal hypoxia in mammals causes fetal growth restriction and catecholaminergic overstimulation that, in turn, alter signaling pathways associated with adrenergic receptors. Beta-adrenoceptors (beta-ARs) are essential for fetal cardiac development and regulation of cardiac contractility. We studied the effects of chronic prenatal hypoxia on cardi...