Publications by authors named "I Braren"
Article Synopsis
- - Hypertrophic cardiomyopathy (HCM) is a common genetic heart disorder linked to sarcomere gene mutations, resulting in left ventricular thickening and diastolic dysfunction; new research emphasizes the importance of microtubule alterations in heart failure.
- - The study explored the effects of increasing tubulin tyrosination via adeno-associated virus transfer in various models, including HCM human cardiomyocytes and specific mouse models, revealing that this approach improved heart function by reducing harmful microtubule modifications and enhancing contractility.
- - Results indicated that enhancing tubulin tyrosination led to better heart function metrics such as contractility and cardiac output in both human and mouse models, while also suggesting potential benefits of targeting the micro
Objective: Recombinant adeno-associated virus (rAAV) vectors are powerful tools for the sustained expression of proteins in vivo and have been successfully used for mechanistic studies in mice. A major challenge associated with this method is to obtain tissue specificity and high expression levels without need of local virus administration.
Methods: To achieve this goal for brown adipose tissue (BAT), we developed a rAAV vector for intravenous bolus injection, which includes an expression cassette comprising an uncoupling protein-1 enhancer-promoter for transcription in brown adipocytes and miR122 target sequences for suppression of expression in the liver, combined with packaging in serotype Rec2 capsid protein.
Hypertrophic cardiomyopathy (HCM) is the most common cardiac genetic disorder caused by sarcomeric gene variants and associated with left ventricular (LV) hypertrophy and diastolic dysfunction. The role of the microtubule network has recently gained interest with the findings that -α-tubulin detyrosination (dTyr-tub) is markedly elevated in heart failure. Acute reduction of dTyr-tub by inhibition of the detyrosinase (VASH/SVBP complex) or activation of the tyrosinase (tubulin tyrosine ligase, TTL) markedly improved contractility and reduced stiffness in human failing cardiomyocytes, and thus poses a new perspective for HCM treatment.
View Article and Find Full Text PDFRegulation of systemic PCO is a life-preserving homeostatic mechanism. In the medulla oblongata, the retrotrapezoid nucleus (RTN) and rostral medullary Raphe are proposed as CO chemosensory nuclei mediating adaptive respiratory changes. Hypercapnia also induces active expiration, an adaptive change thought to be controlled by the lateral parafacial region (pF).
View Article and Find Full Text PDFArticle Synopsis
- The study investigates the effects of a missense genetic variant in the ACTN2 gene, linked to various forms of cardiomyopathy, particularly hypertrophic cardiomyopathy.
- Using CRISPR/Cas9, researchers created two types of human stem cell-derived cardiomyocyte lines to compare the normal and mutated ACTN2 genes.
- Results showed that the mutated ACTN2 led to structural and functional issues in cardiomyocytes, including increased multinucleation and protein aggregation, and activated proteolytic systems to manage these problems, suggesting a link to cardiac diseases.