Pregnancy-Associated Plasma Protein-A Accelerates Atherosclerosis by Regulating Reverse Cholesterol Transport and Inflammation

Abstract

Background:Recent studies have suggested that pregnancy-associated plasma protein-A (PAPP-A) is involved in the pathogenesis of atherosclerosis. This study aim is to investigate the role and mechanisms of PAPP-A in reverse cholesterol transport (RCT) and inflammation during the development of atherosclerosis. Methods and Results:PAPP-A was silenced in apolipoprotein E (apoE −/− ) mice with administration of PAPP-A shRNA. Oil Red O staining of the whole aorta root revealed that PAPP-A knockdown reduced lipid accumulation in aortas. Oil Red O, hematoxylin and eosin (HE) and Masson staining of aortic sinus further showed that PAPP-A knockdown alleviated the formation of atherosclerotic lesions. It was found that PAPP-A knockdown reduced the insulin-like growth factor 1 (IGF-1) levels and repressed the PI3K/Akt pathway in both aorta and peritoneal macrophages. The expression levels of LXRα, ABCA1, ABCG1, and SR-B1 were increased in the aorta and peritoneal macrophages from apoE −/− mice administered with PAPP-A shRNA. Furthermore, PAPP-A knockdown promoted RCT from macrophages to plasma, the liver, and feces in apoE −/− mice. In addition, PAPP-A knockdown elevated the expression and secretion of monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), tumor necrosis factor-α, and interleukin-1β through the nuclear factor kappa-B (NF-κB) pathway. Conclusions:The present study results suggest that PAPP-A promotes the development of atherosclerosis in apoE −/− mice through reducing RCT capacity and activating an inflammatory response.

Hsa-circ_0010283 Regulates Oxidized Low-Density Lipoprotein-Induced Proliferation and Migration of Vascular Smooth Muscle Cells by Targeting the miR-133a-3p/Pregnancy-Associated Plasma Protein A Axis

“…Pregnancy-associated plasma protein A (PAPPA) has served as an indicator of cardiovascular events, and PAPPA promoted the expression of inflammatory markers, thus triggering atherosclerosis. 16,17 In addition, PAPPA also participated in the regulation of proliferation and apoptosis of ox-LDL-treated VSMCs, 10 whereas the mechanism of PAPPA action in VSMCs is not been completely understood.…”

CTRP12 ameliorates atherosclerosis by promoting cholesterol efflux and inhibiting inflammatory response via the miR-155-5p/LXRα pathway

“…After forming an obligate heterodimer with retinoid X receptor, LXRα binds to LXR-response elements in the promoter of ABCA1 and ABCG1 genes to stimulate their transcription 49 . Studies from our group and others have revealed that angiopoietin-1, pregnancyassociated plasma protein-A, and homocysteine inhibit ABCA1-and ABCG1-dependent cholesterol efflux from lipid-loaded macrophages and aggravate atherosclerosis in apoE −/− mice by downregulating LXRα expression [50][51][52] . As a pleiotropic miRNA, miR-155-5p is linked to metabolic diseases, such as diet-induced obesity 53 and diabetes 54 .…”

Investigation of pregnancy associated plasma protein‐A and neopterin levels in Behçet's patients

“…There is no parameter to clearly show the diagnosis and activity of BD. 8 This study showed that neopterin and hsCRP increased in Behçet 0 s patients, while PAPP-A did 20 Biomarkers such as hsCRP are also used to assess the contribution of inflammation in the pathophysiology of atherosclerosis and to predict primary cardiovascular risks. 21 In a study between pregnant Behçet's patients and healthy pregnant women, no significant difference was found between PAPP-A levels.…”

“…It is known that PAPP‐A levels elevate in ruptured plaques and PAPP‐A trigger thrombotic events. Some investigators suggested PAPP‐A as a new marker for acute coronary syndrome 20 . Biomarkers such as hsCRP are also used to assess the contribution of inflammation in the pathophysiology of atherosclerosis and to predict primary cardiovascular risks 21 .…”