Heart failure is a serious medical condition with a poor prognosis. Current treatments can only help manage the symptoms and slow the progression of heart failure. However, there is currently no cure to prevent and reverse cardiac remodeling.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Basis Dis
June 2023
Heart formation requires transcriptional regulators that underlie congenital anomalies and the fetal gene program activated during heart failure. Attributing the effects of congenital heart disease (CHD) missense variants to disruption of specific protein domains allows for a mechanistic understanding of CHDs and improved diagnostics. A combined chemical and genetic approach was employed to identify novel CHD drivers, consisting of chemical screening during pluripotent stem cell (PSC) differentiation, gene expression analyses of native tissues and primary cell culture models, and the in vitro study of damaging missense variants from CHD patients.
View Article and Find Full Text PDFThe procholecystokinin (proCCK) gene encodes a secreted peptide known to regulate the digestive, endocrine, and nervous systems. Though recently proposed as a biomarker for heart dysfunction, its physiological role in both the embryonic and adult heart is poorly understood, and there are no reports of tissue-specific regulators of cholecystokinin signaling in the heart or other tissues. In the present study, mRNA of proCCK was observed in cardiac tissues during mouse embryonic development, establishing proCCK as an early marker of differentiated cardiomyocytes which is later restricted to anatomical subdomains of the neonatal heart.
View Article and Find Full Text PDFACS Appl Mater Interfaces
February 2020
Heart tissue engineering is critical in the treatment of myocardial infarction, which may benefit from drug-releasing smart materials. In this study, we load a small molecule (3i-1000) in new biodegradable and conductive patches for application in infarcted myocardium. The composite patches consist of a biocompatible elastomer, poly(glycerol sebacate) (PGS), coupled with collagen type I, used to promote cell attachment.
View Article and Find Full Text PDFReliable in vitro models to assess developmental toxicity of drugs and chemicals would lead to improvement in fetal safety and a reduced cost of drug development. The validated embryonic stem cell test (EST) uses cardiac differentiation of mouse embryonic stem cells (mESCs) to predict in vivo developmental toxicity, but does not take into account the stage-specific patterning of progenitor populations into anterior (ventricular) and posterior (atrial) compartments. In this study, we generated a novel dual reporter mESC line with fluorescent reporters under the control of anterior and posterior cardiac promoters.
View Article and Find Full Text PDFVarious strategies have been applied to replace the loss of cardiomyocytes in order to restore reduced cardiac function and prevent the progression of heart disease. Intensive research efforts in the field of cellular reprogramming and cell transplantation may eventually lead to efficient in vivo applications for the treatment of cardiac injuries, representing a novel treatment strategy for regenerative medicine. Modulation of cardiac transcription factor (TF) networks by chemical entities represents another viable option for therapeutic interventions.
View Article and Find Full Text PDFTranscription factors are pivotal regulators of gene transcription, and many diseases are associated with the deregulation of transcriptional networks. In the heart, the transcription factors GATA4 and NKX2-5 are required for cardiogenesis. GATA4 and NKX2-5 interact physically, and the activation of GATA4, in cooperation with NKX2-5, is essential for stretch-induced cardiomyocyte hypertrophy.
View Article and Find Full Text PDFChronic heart failure, predominantly developed after myocardial infarction, is a leading cause of high mortality worldwide. As existing therapies have still limited success, natural and/or synthetic nanomaterials are emerging alternatives for the therapy of heart diseases. Therefore, we aimed to functionalize undecylenic acid thermally hydrocarbonized porous silicon nanoparticles (NPs) with different targeting peptides to improve the NP's accumulation in different cardiac cells (primary cardiomyocytes, non-myocytes, and H9c2 cardiomyoblasts), additionally to investigate the behavior of the heart-targeted NPs in vivo.
View Article and Find Full Text PDFMyocardial infarction (MI), commonly known as a heart attack, is the irreversible necrosis of heart muscle secondary to prolonged ischemia, which is an increasing problem in terms of morbidity, mortality and healthcare costs worldwide. Along with the idea to develop nanocarriers that efficiently deliver therapeutic agents to target the heart, in this study, we aimed to test the in vivo biocompatibility of different sizes of thermally hydrocarbonized porous silicon (THCPSi) microparticles and thermally oxidized porous silicon (TOPSi) micro and nanoparticles in the heart tissue. Despite the absence or low cytotoxicity, both particle types showed good in vivo biocompatibility, with no influence on hematological parameters and no considerable changes in cardiac function before and after MI.
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