What was already known?

Systemic Lupus Erythematosus (SLE, or just “lupus”) is an autoimmune disease which can affect any part of the body.  Patients with SLE have a higher risk of developing heart disease. This is partly due problems repairing damaged blood vessels. Myeloid angiogenic cells (MACs), which are found in the blood, have an important role in helping blood vessels repair. The function of these cells is known to be reduced in patients with SLE.

Recently some studies have suggested that low vitamin D may be an important contributor to the development of heart disease. Vitamin D deficiency is common in patients with SLE. In this study we investigated the effects of vitamin D on MACs and how the blood vessels of SLE patients responded when low vitamin D was corrected.

What was discovered?

The number of MACs was increased in patients with SLE compared to healthy controls. However the MACs from SLE patients did not function as well as those from healthy controls. We used a number of different methods to look at how MACs responded to vitamin D treatment. After treatment with vitamin D, the MACs from SLE patients (with vitamin D deficiency) behaved more like healthy MACs.

In addition, the MACs from SLE patients produced an increased amount of a protein (cytokine) called CXCL-10 which inhibits blood vessel repair. Vitamin D reduced the production of CXCL-10 which in turn increased the beneficial effects of MACs on blood vessel cells.

Finally, vitamin D improved the ability of MACs to encourage blood vessel cells to produce nitric oxide synthase, an enzyme important for blood vessel function.

We used a technique called flow-mediated dilatation (FMD) to look at the ability of blood vessels to respond to stress. In SLE patients, treatment of vitamin D deficiency resulted in an improvement in FMD over a 3 month period, whereas there was no change in patients with normal levels of vitamin D. This effect was not related to changes in SLE symptoms/disease activity or other factors such as blood pressure.

Why is this important? What is the benefit to patients?

This is the first study to show that treating low vitamin D in SLE patients can improve blood vessel health. Furthermore we identified that this effect may be due to changes in MAC function and therefore blood vessel repair.

The results of this study suggest that vitamin D could be a cheap and relatively safe way to reduce heart disease in SLE patients. A clinical trial of vitamin D is now needed to determine whether vitamin D can significantly reduce heart disease in SLE. In addition, this study suggests that other ways to improve blood vessel repair in SLE should be investigated.

Publications

(Reynolds JA et al. (2016). Vitamin D improves endothelial dysfunction and restores myeloid angiogenic cell function via reduced CXCL-10 expression in systemic lupus erythematosus. Scientific Reports 6, Article number: 22341, PMID:26930567| DOI:10.1038/srep22341)

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