ArticleBioMed research international2015
SERCA2 Haploinsufficiency in a Mouse Model of Darier Disease Causes a Selective Predisposition to Heart Failure.
Article in BioMed research international, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- Gene and drug-mediated SERCA2a activation restores cardiac function and metabolic balance in diabetic mice.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- Review
- Pumping the Breaks on Acantholytic Skin Disorders: Targeting Calcium Pumps, Desmosomes, and Downstream Signaling in Darier, Hailey-Hailey, and Grover Disease.The Journal of investigative dermatology · 2025Review
- Cardiac-Specific Expression of Cre Recombinase Leads to Age-Related Cardiac Dysfunction Associated with Tumor-like Growth of Atrial Cardiomyocyte and Ventricular Fibrosis and Ferroptosis.International journal of molecular sciences · 2023Article
- Darier Disease - A Multi-organ Condition?Acta dermato-venereologica · 2021Review
- Darier disease is associated with heart failure: a cross-sectional case-control and population based study.Scientific reports · 2020Article
- Primary Active CaCold Spring Harbor perspectives in biology · 2020Review
- Article
- SERCA2 Deficiency Impairs Pancreatic β-Cell Function in Response to Diet-Induced Obesity.Diabetes · 2016Article
- Loss of Mouse P2Y6 Nucleotide Receptor Is Associated with Physiological Macrocardia and Amplified Pathological Cardiac Hypertrophy.The Journal of biological chemistry · 2016Article
- Calcium-ATPases: Gene disorders and dysregulation in cancer.Biochimica et biophysica acta · 2016Review
- Downregulation of GSTK1 Is a Common Mechanism Underlying Hypertrophic Cardiomyopathy.Frontiers in pharmacology · 2016Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Null mutations in one copy of ATP2A2, the gene encoding sarco/endoplasmic reticulum Ca(2+)-ATPase isoform 2 (SERCA2), cause Darier disease in humans, a skin condition involving keratinocytes. Cardiac function appears to be unimpaired in Darier disease patients, with no evidence that SERCA2 haploinsufficiency itself causes heart disease. However, SERCA2 deficiency is widely considered a contributing factor in heart failure. We therefore analyzed Atp2a2 heterozygous mice to determine whether SERCA2 haploinsufficiency can exacerbate specific heart disease conditions. Despite reduced SERCA2a levels in heart, Atp2a2 heterozygous mice resembled humans in exhibiting normal cardiac physiology. When subjected to hypothyroidism or crossed with a transgenic model of reduced myofibrillar Ca(2+)-sensitivity, SERCA2 deficiency caused no enhancement of the disease state. However, when combined with a transgenic model of increased myofibrillar Ca(2+)-sensitivity, SERCA2 haploinsufficiency caused rapid onset of hypertrophy, decompensation, and death. These effects were associated with reduced expression of the antiapoptotic Hax1, increased levels of the proapoptotic genes Chop and Casp12, and evidence of perturbations in energy metabolism. These data reveal myofibrillar Ca(2+)-sensitivity to be an important determinant of the cardiac effects of SERCA2 haploinsufficiency and raise the possibility that Darier disease patients are more susceptible to heart failure under certain conditions.
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