Overexpression of tissue-nonspecific alkaline phosphatase (TNAP) in endothelial cells accelerates coronary artery disease in a mouse model of familial hypercholesterolemia

• Published in: PloS one 2017-10, Vol.12 (10), p.e0186426-e0186426
• Main Authors: Romanelli, Filippo, Corbo, AnthonyMarco, Salehi, Maryam, Yadav, Manisha C, Salman, Soha, Petrosian, David, Rashidbaigi, Omid J, Chait, Jesse, Kuruvilla, Jes, Plummer, Maria, Radichev, Ilian, Margulies, Kenneth B, Gerdes, A Martin, Pinkerton, Anthony B, Millán, José Luis, Savinov, Alexei Y, Savinova, Olga V
• Format: Article
• Language: English
• Subjects: Alizarin; Alkaline phosphatase; Alkaline Phosphatase - antagonists & inhibitors; Alkaline Phosphatase - genetics; Alkaline Phosphatase - metabolism; Animal models; Animal tissues; Animals; Arteries; Arteriosclerosis; Atherosclerosis; Biology and Life Sciences; Blood Chemical Analysis; Body weight; Body Weight - drug effects; Calcification; Calcification (ectopic); Calcification, Physiologic; Calcium; Cardiovascular disease; Care and treatment; Cells, Cultured; Core Binding Factor Alpha 1 Subunit - genetics; Core Binding Factor Alpha 1 Subunit - metabolism; Cores; Coronary artery; Coronary artery disease; Coronary Artery Disease - etiology; Coronary heart disease; Coronary vessels; Coronary Vessels - metabolism; Coronary Vessels - pathology; Cre recombinase; Cytokines - blood; Deposition; Diagnosis; Diet, Atherogenic; Disease Models, Animal; Echocardiography; Endothelial cells; Endothelial Cells - cytology; Endothelial Cells - metabolism; Endothelium; Endothelium, Vascular - enzymology; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Enzyme Inhibitors - pharmacology; Foams; Genetic aspects; Heart; Heart diseases; Heart failure; Humans; Hypercholesterolemia; Hyperlipoproteinemia Type II - metabolism; Hyperlipoproteinemia Type II - pathology; Immunohistochemistry; Ischemia; Laboratory animals; Lesions; Lipids; Lipoprotein (low density) receptors; Low density lipoprotein receptors; Medical research; Medicine; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mineralization; Mutation; Myocardium; Myocardium - enzymology; Myocardium - metabolism; Myocardium - pathology; Osteopathic medicine; Pharmacology; Phosphatase; Placebo Effect; Receptor density; Receptors, LDL - genetics; Recombinase; Research and Analysis Methods; Smooth muscle; Thickening; Thrombosis; Ventricle; Ventricular Function, Left - drug effects; Weight reduction
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0186426

Overexpression of tissue-nonspecific alkaline phosphatase (TNAP) in endothelium leads to arterial calcification in mice. The purpose of this study was to examine the effect of elevated endothelial TNAP on coronary atherosclerosis. In addition, we aimed to examine endogenous TNAP activity in human myocardium. A vascular pattern of TNAP activity was observed in human non-failing, ischemic, and idiopathic dilated hearts (5 per group); no differences were noted between groups in this study. Endothelial overexpression of TNAP was achieved in mice harboring a homozygous recessive mutation in the low density lipoprotein receptor (whc allele) utilizing a Tie2-cre recombinase (WHC-eTNAP mice). WHC-eTNAP developed significant coronary artery calcification at baseline compared WHC controls (4312 vs 0μm2 alizarin red area, p