title: Cardiac hypertrophy and decreased high-density lipoprotein cholesterol in Lrig3-deficient mice.
abstract: Genetic factors confer risk for cardiovascular disease. Recently, large genome-wide population studies have shown associations between genomic loci close to LRIG3 and heart failure and plasma high-density lipoprotein (HDL) cholesterol level. Here, we ablated Lrig3 in mice and investigated the importance of Lrig3 for heart function and plasma lipid levels. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to analyze Lrig3 expression in the hearts of wild-type and Lrig3-deficient mice. In addition, molecular, physiological, and functional parameters such as organ weights, heart rate, blood pressure, heart structure and function, gene expression in the heart, and plasma insulin, glucose, and lipid levels were evaluated. The Lrig3-deficient mice were smaller than the wild-type mice but otherwise appeared grossly normal. Lrig3 was expressed at detectable but relatively low levels in adult mouse hearts. At 9 mo of age, ad libitum-fed Lrig3-deficient mice had lower insulin levels than wild-type mice. At 12 mo of age, Lrig3-deficient mice exhibited increased blood pressure, and the Lrig3-deficient female mice displayed signs of cardiac hypertrophy as assessed by echocardiography, heart-to-body weight ratio, and expression of the cardiac hypertrophy marker gene Nppa. Additionally, Lrig3-deficient mice had reduced plasma HDL cholesterol and free glycerol. These findings in mice complement the human epidemiological results and suggest that Lrig3 may influence heart function and plasma lipid levels in mice and humans.
authors.affiliation: Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden; martin.hellstrom@onkologi.umu.se.
authors.forename: Martin
authors.initials: M
authors.lastname: Hellström
authors.affiliation: Department of Medical Biosciences, Physiological Chemistry, Umeå University, Umeå, Sweden;
authors.forename: Madelene
authors.initials: M
authors.lastname: Ericsson
authors.affiliation: Department of Public Health and Clinical Medicine, Medicine, Umeå University, Umeå, Sweden; and.
authors.forename: Bengt
authors.initials: B
authors.lastname: Johansson
authors.affiliation: Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden;
authors.forename: Mahmood
authors.initials: M
authors.lastname: Faraz
authors.affiliation: Department of Medical Biosciences, Physiological Chemistry, Umeå University, Umeå, Sweden;
authors.forename: Fredrick
authors.initials: F
authors.lastname: Anderson
authors.affiliation: Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden; Regional Cancer Center Stockholm/Gotland, Stockholm, Sweden.
authors.forename: Roger
authors.initials: R
authors.lastname: Henriksson
authors.affiliation: Department of Medical Biosciences, Physiological Chemistry, Umeå University, Umeå, Sweden;
authors.forename: Stefan K
authors.initials: SK
authors.lastname: Nilsson
authors.affiliation: Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden;
authors.forename: Håkan
authors.initials: H
authors.lastname: Hedman
mesh_terms: D000818:Animals; D001794:Blood Pressure; D006332:Cardiomegaly / Q000503:physiopathology*; D008076:Cholesterol, HDL / Q000097:blood*; D015536:Down-Regulation; D005260:Female; D006321:Heart; D006339:Heart Rate; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000473:pathology*
chemical_list: D008076:Cholesterol, HDL; C496407:Lrig3 protein, mouse; D008565:Membrane Proteins
keywords: cholesterol; heart; hypertrophy; leucine-rich repeats and immunoglobulin-like domains 3; mice