Why plaque develop in artery, not in vein?

 In medical community there is a group of clinicians who believe Low Density Lipoprotein (LDL) is major cause of atherosclerosis, while another group of clinicians believe LDL is not the cause of atherosclerosis. Confusing right? This article will provide insight on this ongoing debate in medical community.

Argument proposed by clinicians who believe LDL is not the major cause of atherosclerosis:

If LDL is causative risk factor for heart disease, why do we only see plaque in arteries not in vein?

Seems legit point. Even if vein is part of same circulation, it receives same blood so it should have same exposure of LDL as to arteries. This is a great question. We are going to address this in this article.

                  

           

Figure: Comparison of structure of artery vs vein¹

Artery and vein have almost identical structure. Also, LDL is also same in circulation then it makes logical sense that vein would also have atherosclerosis.

Argument by clinicians who believes LDL is the major cause of atherosclerosis:

Plenty of studies have done which indicate LDL is associated to heart disease due to its movement from bloodstream past the lining of cells-endothelial cells². The reason why it gets attracted to subendothelial cell- below endothelial cell is because Apo B is attracted to charged molecule called proteoglycan, which is found in high concentration in sub endothelium, once they bind to one another LDL gets retained^3,4.

 

So, if all of this is true then why there is exception for vein?

ü  Vein has endothelial cells

ü  Vein has same exposure to LDL

ü  They have same proteoglycan- correct, but how much of proteoglycan exist in artery vs vein?

Structure of proteoglycan:

 

 

 

 

 

 

 

Proteoglycan is made up of protein backbone and glycosaminoglycan (CAG), there are different types of CAG which retain LDL differently. According to study arteries have very much high level of certain CAGs compared to veins. The most abundant glycosaminoglycan in human vein is dermatan sulfate, whereas chondroitin 4/6-sulfate is preponderant in arteries⁵.

It is known that certain glycosaminoglycan species from the arterial wall, mainly high-molecular-weight fractions of dermatan sulfate + chondroitin 4/6-sulfate have greater affinity for plasma LDL. So this explains why major plaque formation site is artery.

                                      

This small but significant difference make artery more susceptible to plaque formation compared to vein.

 

References:

1.     Downtown Vein Treatment Center. Artery vs. Vein: What’s the difference? [Internet]. Downtown Vein & Vascular. 2023 [cited 2024 Jul 17]. Available from: https://www.downtownveinvascular.com/artery-vs-vein-whats-the-difference/

2.     Linton MF, Yancey PG, Davies SS, Gray Jerome W, Linton EF, Song WL, et al. The role of lipids and lipoproteins in atherosclerosis. MDText.com; 2019.

3.     Shapiro MD, Fazio S. Apolipoprotein B-containing lipoproteins and atherosclerotic cardiovascular disease. F1000Res [Internet]. 2017 [cited 2024 Jul 17];6:134. Available from: http://dx.doi.org/10.12688/f1000research.9845.1

4.     Behbodikhah J, Ahmed S, Elyasi A, Kasselman LJ, De Leon J, Glass AD, et al. Apolipoprotein B and cardiovascular disease: Biomarker and potential therapeutic target. Metabolites [Internet]. 2021 [cited 2024 Jul 17];11(10):690. Available from: http://dx.doi.org/10.3390/metabo11100690

5.     Leta GC, Mourão PAS, Tovar AMF. Human venous and arterial glycosaminoglycans have similar affinity for plasma low-density lipoproteins. Biochim Biophys Acta Mol Basis Dis [Internet]. 2002;1586(3):243–53. Available from: http://dx.doi.org/10.1016/s0925-4439(01)00102-8