Cardiotrophin-1 Deficiency Abrogates Atherosclerosis Progression.
Kapka MitevaDaniela BaptistaFabrizio MontecuccoMohamed AsrihFabienne BurgerAline RothRodrigo A Fraga-SilvaNikolaos StergiopulosFrançois MachKarim J BrandtPublished in: Scientific reports (2020)
Cardiotrophin-1 (CT-1) is associated with cardiovascular (CV) diseases. We investigated the effect of CT-1 deficiency in the development and progression of atherosclerosis in double knockout Apoe-/-ct-1-/- mice. Apoe-/- C57Bl/6 or Apoe-/-ct-1-/- C57Bl/6 mice were fed a normal chow diet (NCD) or a high-cholesterol diet (HCD). After sacrifice, serum triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), free fatty acids and systemic paracrine factors were measured. Intraplaque lipid and collagen content were quantified in the aortic sections. Immune cell populations in spleen, lymph nodes and aorta were analysis by flow cytometry. Apoe-/-ct-1-/- mice in accelerated atherosclerosis exhibited a reduction of total cholesterol, LDL-C, atherosclerotic plaques size in the aortic root and in the abdominal aorta and improved plaque stability in comparison to Apoe-/- mice. CT-1 deficiency in Apoe-/- mice on (HCD) promoted atheroprotective immune cell responses, as demonstrated by a rise in plasma anti-inflammatory immune cell populations (regulatory T cells, Tregs; regulatory B cells, Bregs and B1a cells) and atheroprotective IgM antibodies. CT-1 deficiency in advanced atherosclerosis mediated regulation of paracrine factors, such as interleukin (IL)-3, IL-6, IL-9, IL-15, IL-27, CXCL5, MCP-3, MIP-1α and MIP-1β. In a model of advanced atherosclerosis, CT-1 deficiency induced anti-inflammatory and atheroprotective effects which resulted in abrogation of atheroprogression.
Keyphrases
- image quality
- dual energy
- computed tomography
- contrast enhanced
- cognitive decline
- regulatory t cells
- high fat diet
- cardiovascular disease
- positron emission tomography
- high fat diet induced
- aortic valve
- anti inflammatory
- lymph node
- magnetic resonance imaging
- physical activity
- pulmonary artery
- fatty acid
- coronary artery disease
- low density lipoprotein
- replacement therapy
- insulin resistance
- type diabetes
- flow cytometry
- cell proliferation
- left ventricular
- induced apoptosis
- weight loss
- early stage
- adipose tissue
- atrial fibrillation
- oxidative stress
- diabetic rats
- transcription factor
- mass spectrometry
- mild cognitive impairment
- high resolution
- atomic force microscopy