ABSTRACT
Several studies have demonstrated the expression of odorant receptors (OR) in various human tissues and their involvement in different physiological and pathophysiological processes. However, the functional role of ORs in the human heart is still unclear. Here, we firstly report the functional characterization of an OR in the human heart. Initial next-generation sequencing analysis revealed the OR expression pattern in the adult and fetal human heart and identified the fatty acid-sensing OR51E1 as the most highly expressed OR in both cardiac development stages. An extensive characterization of the OR51E1 ligand profile by luciferase reporter gene activation assay identified 2-ethylhexanoic acid as a receptor antagonist and various structurally related fatty acids as novel OR51E1 ligands, some of which were detected at receptor-activating concentrations in plasma and epicardial adipose tissue. Functional investigation of the endogenous receptor was carried out by Ca2+ imaging of human stem cell-derived cardiomyocytes. Application of OR51E1 ligands induced negative chronotropic effects that depended on activation of the OR. OR51E1 activation also provoked a negative inotropic action in cardiac trabeculae and slice preparations of human explanted ventricles. These findings indicate that OR51E1 may play a role as metabolic regulator of cardiac function.
Subject(s)
Fatty Acids/metabolism , Myocardium/metabolism , Myocytes, Cardiac/metabolism , Neoplasm Proteins/metabolism , Receptors, G-Protein-Coupled/metabolism , Blotting, Western , Cells, Cultured , Gene Knockdown Techniques , High-Throughput Nucleotide Sequencing , Humans , Immunohistochemistry , Immunoprecipitation , Polymerase Chain ReactionSubject(s)
Choroid Diseases/complications , Macular Edema/etiology , Retinal Hemorrhage/etiology , Adult , Choroid Diseases/diagnostic imaging , Fluorescein Angiography , Humans , Macula Lutea/diagnostic imaging , Macular Edema/diagnostic imaging , Male , Radiography , Retinal Hemorrhage/diagnostic imagingABSTRACT
It is suspected that radiation retinopathy is more likely to develop in an eye with preexisting diabetic retinopathy than in a normal eye. However, there is only one report of this occurring, at a radiation dose of 4500 rads. We present a woman with minimal diabetic retinopathy who had breast carcinoma which was treated with chemotherapy but metastasised to the choroid. Within nine months of external beam radiation (3000 rads in fractions of 200 rads) a fulminant retinopathy evolved in that eye, while the non-radiated eye showed no change. The histopathology of radiation and diabetic retinopathy and causes for possible synergism are discussed. As this case report shows, radiation oncologists and ophthalmologists need to be aware of the risk that patients with minimal diabetic retinopathy who have undergone chemotherapy may suffer a dramatic visual loss from radiation therapy despite a radiation dose which is considered adequate, safe, and properly fractionated.
Subject(s)
Choroid Neoplasms/radiotherapy , Diabetic Retinopathy/complications , Radiation Injuries/etiology , Retinal Diseases/etiology , Breast Neoplasms/drug therapy , Choroid Neoplasms/secondary , Female , Fluorescein Angiography , Humans , Middle Aged , Radiotherapy/adverse effects , Radiotherapy DosageABSTRACT
Many patients with branch retinal vein occlusions can develop significant long-term diminution of vision due to such complications as macular edema, retinal neovascularization, and vitreous hemorrhage. One of us (S.C.) developed a new surgical procedure that involves sectioning or decompression of the common sheath connecting the artery and vein at the crossing where a branch retinal vein occlusion occurs. The patient whose case we report had a visual acuity improvement from 20/200-2 to 20/25+1 eight months after surgery.
