A new research from Wake Forest University Baptist Medical Center has provided clues about the causes of lupus and has suggested specific new targeted treatment strategies.
The study was presented at the American College of Rheumatology in Boston.
During the study, researchers looked at premature atherosclerosis in lupus patients as well as accelerated cell death that seems to be behind many of the disease's symptoms.
Previous studies by Mishra found that a new class of drugs being developed (histone deacetylase inhibitors) were effective at preventing atherosclerosis in mice prone to develop the disease.
In the current study, Mishra and colleagues explored whether it is a specific histone deacetylase, number 9 (HDAC9) that causes the problem.
Histones are considered the master regulators in gene expression, and Mishra is the first to establish a link between abnormal histone codes and the complications of lupus in a mouse model of lupus.
The current study has revealed that in atherosclerosis-prone mice, there is more HDAC9 than usual in the macrophages, which are cells within the artery walls that collect cholesterol and can lead to atherosclerosis.
The researchers found that these increased levels of HDAC9 increase inflammation in the arteries as well as the buildup of fatty tissue that may break off and cause a heart attack or stroke.
In mice macrophages that were genetically engineered to have no HDAC9, the research team found the production of chemicals that promote inflammation were reduced and levels of cholesterol deposits were reduced compared to mice that produced normal levels of HDAC9.
"With the drug that inhibits HDAC9, we were able to decrease inflammation and remove cholesterol at the same time. This study suggests that specifically targeting HDAC9 without inhibiting other histone deacetylases will be helpful for atherosclerosis," said Mishra.
In another study, researchers found a potential explanation for why cells in lupus patients die at an increased rate and accumulate in tissues. This accumulation of cells is believed to trigger the inflammation that causes symptoms.
"We have not previously understood why cells die at an increased rate. This new study suggests both a possible mechanism and treatment," said Mishra.
The research team examined microRNAs, chains of ribonucleic acid that are involved in cell proliferation and cell death. The goal was to explore the possibility that aberrant expression of microRNAs is responsible for the abnormal cell death in lupus patients.
The researchers analyzed blood samples from five patients with lupus and seven healthy people of the same ages and sex 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 research team 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.