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Agonistic Autoantibodies to the AT1 Receptor in a Transgenic Rat Model of Preeclampsia
- Source :
- Hypertension. 45:742-746
- Publication Year :
- 2005
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2005.
-
Abstract
- We used rats transgenic for the human angiotensinogen (hAogen) gene and the human renin (hRen) gene and crossed the strains to produce a model of preeclampsia in the dams. The female (n=9) hAogen × male hRen cross had severe (telemetry-measured) hypertension and albuminuria, which developed during the last trimester of pregnancy and subsided after delivery. The converse cross (n=9) and control (n=9) SD rats did not. We demonstrated that the female hAogen × male hRen cross had agonistic antibodies capable of activating the angiotensin (Ang) II AT1 receptor (AT1R-AA) and defined the epitope on the receptor’s second extracellular loop. The phenomenon also occurs in humans with preeclampsia. The rats displayed renal histology reminiscent of preeclampsia, including fibrin deposition confined to the glomeruli. The complement system was activated in glomeruli and IgG deposits were present that may represent AT1R-AA. Finally, we observed an atherosis-like lesion in the spiral arteries of the placental bed, which we called placental-bed arteriolosclerosis. Our model may be relevant to preeclampsia in humans.
- Subjects :
- Male
medicine.medical_specialty
Kidney Glomerulus
Angiotensinogen
Arteriolosclerosis
Biology
Receptor, Angiotensin, Type 1
Immunoglobulin G
Preeclampsia
Animals, Genetically Modified
Rats, Sprague-Dawley
Lesion
Pre-Eclampsia
Pregnancy
Internal medicine
Renin
Renin–angiotensin system
Internal Medicine
medicine
Animals
Humans
Receptor
Complement Activation
Autoantibodies
Fibrin
Angiotensin II receptor type 1
medicine.disease
Rats
Complement system
Endocrinology
biology.protein
Female
medicine.symptom
Subjects
Details
- ISSN :
- 15244563 and 0194911X
- Volume :
- 45
- Database :
- OpenAIRE
- Journal :
- Hypertension
- Accession number :
- edsair.doi.dedup.....f425d8f1a06cb411215f113fcbc6cf61