Transplantation of heterozygous familial hypercholesterolemia living donor liver resulting in early myocardial infarction: a possible dangerous link.

Living donor liver transplantation (LDLT) is a lifesaving procedure that is often curative for several liver diseases. Familial hypercholesterolemia (FH) is a metabolic disease that results from an autosomal dominant mutation in the low-density lipoprotein receptor; yet, young patients with FH can live years without detection. Herein, we report a case of a patient who developed early myocardial infarction (MI) after having a transplant from a donor with undetected heterozygous FH. This was a 67-year-old female with non-alcoholic steatohepatitis-related liver cirrhosis, free from coronary artery disease, who underwent LDLT from her daughter, a 45-year-old female with no past medical history. One year post-transplant, she presented with an acute MI with a large atherosclerotic burden. Genetic analysis confirmed heterozygous FH in the donor but not in the recipient. This case emphasizes the importance of incorporating a thorough clinical history and lipid profile into pre-transplant testing for both the recipient and donor, as well as aggressive lipid-lowering therapy post-transplantation to avoid cardiovascular complications.

Differential Gene Expression Signatures and Cellular Signaling Pathways induced by Lamin A/C Transcript Variants in MCF7 Cell Line.

BACKGROUND: Lamins are the major component of nuclear lamina. Alternative splicing of the 12 exons comprising lamin A/C gene creates five known transcript variants, lamin A, lamin C, lamin AΔ10, lamin AΔ50, and lamin C2. The main objective for this study was to examine the association of critical pathways, networks, molecular and cellular functions regulated by each Lamin A/C transcript variants. METHODS: Ion AmpliSeq Transcriptome Human Gene Expression analysis was performed on MCF7 cells stably transfected with lamin A/C transcript variants. RESULTS: Lamin A or lamin AΔ50 upregulation was associated with activation of cell death and inactivation of carcinogenesis while both lamin C or lamin AΔ10 upregulation activated carcinogenesis and cell death. CONCLUSIONS: Data suggest anti-apoptotic and anti-senescence effects of lamin C and lamin AΔ10 as several functions, including apoptosis and necrosis functions are inactivated following lamin C or lamin AΔ10 upregulation. However, lamin AΔ10 upregulation is associated with a more carcinogenic and aggressive tumor phenotype. Lamin A or lamin AΔ50 upregulation is associated with a predicted activation of increased cell death and inactivation of carcinogenesis. Thus, different signaling pathways, networks, molecular and cellular functions are activated/inactivated by lamin A/C transcript variants resulting in a large number of laminopathies.