Dr Nilamadham Mishra is heading up research at the Wake Forest University Baptist Medical Center into two separate complications of lupus, the premature development of atherosclerosis and the accelerated cell death that seems to be behind many of the disease's symptoms.

It is difficult to estimate how many people suffer from lupus but it is thought around two million people in the US suffer from one form of lupus or another. It can attack virtually any system in the body, including the joints, kidneys, heart, lungs, brain and blood.

Speaking at the American College of Rheumatology in Boston this week, Mishra explained that the team had looked at the potential mechanisms of premature atherosclerosis, which is one of the leading causes of death and disability in lupus patients. Even when they take drugs to lower their cholesterol, lupus patients still develop fatty buildups in their vessels, which can lead to heart attack and stroke.

Mishra was the first to establish a link between abnormal histone codes and the complications of lupus and the researchers had already discovered that histone deacetylase inhibitors were effective at preventing atherosclerosis in mice prone to develop the disease,

In the current study, the researchers were looking at whether it is histone deacetylase 9 (HDAC9) specifically that causes the problem.

They discovered that in atherosclerosis-prone mice, there is more HDAC9 than usual in the macrophages, which are cells within the artery walls that collect cholesterol.

The higher levels of HDAC9 increase inflammation and the build-up of fatty tissue in the arteries. If this breaks off, it can cause a heart attack or stroke.

Conversely, in mice macrophages that were genetically engineered to have no HDAC9, the production of pro-inflammatory chemicals was also reduced along with the levels of cholesterol deposits.

"With the drug that inhibits HDAC9, we were able to decrease inflammation and remove cholesterol at the same time," said Mishra. "This study suggests that specifically targeting HDAC9 without inhibiting other histone deacetylases will be helpful for atherosclerosis."

Increased cell death

In a separate study, the scientists found a potential explanation for why cells in lupus patients die at an increased rate and then accumulate in tissues. This accumulation of cells is believed to trigger the inflammation that causes symptoms.

The study examined microRNAs, in order to explore the possibility that aberrant expression of the molecules is responsible for the abnormal cell death in lupus patients.

The scientists checked blood samples from five patients with lupus and seven healthy people at two points during a three-month period. A particular microRNA, miR-16, was consistently increased in lupus patients compared to the healthy participants. The scientists suspect that having too much miR-16 inhibits genes that control cell death and may also inhibit natural cell progression - resulting in the accumulation in tissues.

"Understanding this connection may lead to targeted treatments to decrease levels of miR-16," said Mishra.