Cross-talk between LOX-1 and PCSK9 in vascular tissues

Ding, Zufeng; Liu, Shijie; Wang, Xianwei; Deng, Xiaoyan; Fan, Yubo; Jiwani, Shahanawaz; Reis, Robert J. Shmookler; Varughese, Kattayi I.; Sawamura, Tatsuya; Mehta, Jawahar L.

doi:10.1093/cvr/cvv178

Cited by 206 publications

(229 citation statements)

References 28 publications

Supporting

Mentioning

218

Contrasting

Unclassified

Order By: Relevance

“…It is known that mitochondria‐derived ROS (mtROS) is the major source of cellular ROS. hPCSK9 can increase the generation of ROS and mtROS in LPS‐treated VSMCs in a concentration‐dependent fashion (Ding et al, , , ). Conversely, PCSK9 knockdown in VSMCs significantly reduced ROS and mtROS production and p‐NF‐κBp65 expression.…”

Section: Pcsk9 and Inflammation In Atherosclerosismentioning

confidence: 99%

PCSK9: A novel inflammation modulator in atherosclerosis?

Tang

Peng

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

Proprotein convertase subtilisin/kexin 9 (PCSK9) is the ninth member of the secretory serine protease family. It binds to low‐density lipoprotein receptor (LDLR) for endocytosis and lysosome degradation in the liver, resulting in an increasing in circulating LDL‐cholesterol (LDL‐c) level. Since a PCSK9 induced increase in plasma LDL‐c contributes to atherosclerosis, PCSK9 inhibition has become a new strategy in preventing and treating atherosclerosis. However, in addition to the effect of PCSK9 on elevating blood LDL‐c levels, accumulating evidence shows that PCSK9 plays an important role in inflammation, likely representing another major mechanism for PCSK9 to promote atherosclerosis. In this review, we discuss the association of PCSK9 and inflammation, and highlight the specific effects of PCSK9 on different vascular cellular components involved in the atherosclerotic inflammation. We also discuss the clinical evidence for the association between PCSK9 and inflammation in atherosclerotic cardiovascular disease. A better understanding of the direct association of PCSK9 with atherosclerotic inflammation might help establish a new role for PCSK9 in vascular biology and identify a novel molecular mechanism for PCSK9 therapy.

show abstract

Section: Pcsk9 and Inflammation In Atherosclerosismentioning

confidence: 99%

PCSK9: A novel inflammation modulator in atherosclerosis?

Tang

Peng

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…In LDLR −/− mice fed a high cholesterol diet, atherosclerosis and arterial wall inflammation are reduced with deletion of LOX-1 52, 53) . Interestingly, the crosstalk between PCSK9 expression and LOX-1 in VSMC leads to a feed-forward loop where PCSK9 stimulates transcription of LOX-1 and LOX-1 activation stimulates PCSK9 expression 54) . The interaction between PCSK9 and LOX-1 may facilitate atherogenesis, particularly during inflammatory states.…”

Section: Pcsk9 and Inflammationmentioning

confidence: 99%

PCSK9 and Atherosclerosis - Lipids and Beyond

Shapiro

Fazio

2017

J Atheroscler Thromb

View full text Add to dashboard Cite

Even though it is only a little over a decade from the discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) as a plasma protein that associates with both high and low cholesterol syndromes, a rich body of knowledge has developed, and drugs inhibiting this target have been approved in many markets. While the majority of research in recent years has focused on the impact of therapeutic antagonism of this molecule, important lines of investigation have emerged characterizing its unique physiology as it relates to cholesterol metabolism and atherosclerosis. The PCSK9 story is unfolding rapidly but is far from complete. One chapter that is of particular interest is the possible direct link between PCSK9 and atherosclerosis. This review specifically examines this relationship drawing from data produced from experimental models of plaque biology and inflammation, atherosclerosis imaging studies, and observational epidemiology.

show abstract

“…It was also suggested that PCSK9 enzyme function is associated with exacerbated inflammatory response in hypercholesterolemia, and atherogenesis. Ding et al (, ) observed a positive interaction between PCSK9 and Lectin‐like ox‐LDL receptor‐1 (LOX‐1), both involved in inflammation, which has important implications in several chronic inflammatory diseases. Pre‐inflammatory factors like lipopolysaccharide (LPS), inflammatory cytokines, tumor necrosis factor‐α, and ox‐LDL proportionately induce PCSK9 expression through reactive oxygen species (ROS) and nuclear factor κB activation in vascular smooth muscle cells (SMCs), and endothelial cells (ECs).…”

Section: Role Of Pcsk9 In Lipid Metabolismmentioning

confidence: 99%

PCSK9 and infection: A potentially useful or dangerous association?

Khademi

Momtazi‐Borojeni

Reiner

et al. 2017

Journal Cellular Physiology

View full text Add to dashboard Cite

Elevated plasma low-density lipoprotein-cholesterol (LDL-C) concentration is the most important risk factor for atherosclerotic cardiovascular diseases (CVDs). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a ubiquitously expressed serine proteinase which plays a key role in cholesterol metabolism, but has been found to be implicated in some other lipid-independent physiological processes. In this review, the role of PCSK9 was evaluated not only concerning lipid metabolism but also hepatitis C virus (HCV) infection, bacterial infections/sepsis, and septic shock. Collected data from clinical trials revealed that treatment with PCSK9 inhibitors has beneficial effects in lowering LDL-C via inhibition of LDL-receptors (LDL-R), an antiviral effect on HCV infection via down-regulating the surface expression of LDL-R and CD81 on hepatic cells, and a positive association with increased inflammatory responses, as well as with septic shock by down-regulation of hepatocyte LDL-R. On the other hand, PCSK9 inhibition by therapeutic fully humanized antibodies has positive effects in reducing elevated LDL-C. However, their safety and tolerability is an important issue which has to be taken into consideration.

show abstract

Cross-talk between LOX-1 and PCSK9 in vascular tissues

Abstract: These observations suggest that LOX-1 and PCSK9 positively influence each other's expression, especially during an inflammatory reaction. mtROS appear to be important initiators of PCSK9/LOX-1 expression.

Cited by 206 publications

References 28 publications

PCSK9: A novel inflammation modulator in atherosclerosis?

PCSK9: A novel inflammation modulator in atherosclerosis?

PCSK9 and Atherosclerosis - Lipids and Beyond

PCSK9 and infection: A potentially useful or dangerous association?

Contact Info

Product

Resources

About