Gene mutation that can lead to heart disease identified
For the first time, scientists have discovered how a gene mutation can cause heart disease in adults despite normal cholesterol levels and no other risk factors.
Researchers at the University of Texas Health Science Center at Houston (UTHealth Houston) have identified a mutation in the ACTA2 gene that can cause calcium to clog artery walls, which can cause coronary artery disease (CAD) to develop in adults as young as 30 years of age.
“The gene ACTA2 codes a specific protein that has nothing to do with cholesterol,” said Dr Dianna Milewicz, senior author of the study and professor and director of the Division of Medical Genetics at McGovern Medical School at UTHealth Houston. “It was a surprise to find that people with the gene mutation had too much atherosclerosis at a young age and with no risk factors.”
While Dr Milescz has previously linked several genetic mutations in ACTA2 to the early onset of CAD, this research has uncovered just how it occurs.
Atherosclerosis is a buildup on the artery walls, often of cholesterol or other fats that can lie dormant until a heart attack or stroke occurs. With this mutation in ACTA2, a gene generally found in the smooth muscle cells that line the arteries, an incorrectly folded protein then leads to cell stress. This in turn leads to cholesterol being produced and plaque forming on the artery walls.
“In our study, the mutant protein made by the ACTA2 mutation caused the cells in the artery wall to be stressed, but there are many other factors that can stress cells,” Dr Milescz said. “We are now working on the risk factors for coronary artery disease, like hypertension, that would also stress the cells and activate this novel pathway for coronary artery disease.
“This finding is unique in that we found a completely new pathway to atherosclerosis,” she added. “It explains why for years we have known statins protect people from heart attacks, even those people whose blood cholesterol levels are normal. In the people with ACTA2 mutations, the statins block the cholesterol made by the stressed smooth muscle cells.”
In the mouse model, the researchers induced atherosclerosis and found that the mice engineered with the ACTA2 mutation had much more atherosclerosis than normal mice in the trial. The study mirrors the human pathway to atherosclerosis.
They also found the condition could be reversed when treated with pravastatin, a member of the statin group of drugs currently used to lower blood cholesterol.
“Cardiac calcium imaging in individuals with ACTA2 mutations could be a useful early diagnostic tool to monitor the development of the early atherosclerosis in these people,” Dr Milewicz said. “This would allow physicians to decide at what age to start these patients on statins.”
While Americans are experiencing fewer heart attacks overall, largely due to medications and better lifestyle choices, CAD is rising in younger adults. In 2019, one in five heart attacks was suffered by someone aged 40 or under.
The study was published in the European Heart Journal.
Source: UTHealth Houston