A recent preclinical study from Weill Cornell Medicine has uncovered new insights into how hypertension, or high blood pressure, can damage the brain well before it causes a noticeable rise in blood pressure.
This research helps explain why hypertension is a major risk factor for cognitive disorders like vascular cognitive impairment and Alzheimer’s disease.
The study, published on November 14 in the journal Neuron, found that hypertension may trigger early changes in gene expression in individual brain cells, leading to problems with thinking and memory. These findings could pave the way for new treatments that not only lower blood pressure but also prevent cognitive decline.
People with hypertension have a 1.2 to 1.5-fold higher risk of developing cognitive disorders compared to those without the condition, but exactly why this happens is not well understood. Even though many medications for hypertension can lower blood pressure, they often do little to improve brain function.
This suggests that blood vessel damage might be occurring independently of the high pressure itself.
Dr. Costantino Iadecola, the senior author of the study and director of the Feil Family Brain and Mind Research Institute at Weill Cornell, explained, “We found that the major cells responsible for cognitive impairment were affected just three days after inducing hypertension in mice—before blood pressure increased. This shows that something beyond the dysregulation of blood pressure is involved.”
The research team used advanced technologies to look at how different types of brain cells were affected at the molecular level. Previously, Dr. Iadecola’s team had found that hypertension affects neurons in the brain, but recent advancements in single-cell technologies allowed them to explore these changes more deeply.
To simulate hypertension in mice, the researchers administered angiotensin, a hormone that raises blood pressure, mimicking the effect in humans.
They then examined how various types of brain cells were impacted at two key points: three days after hypertension was induced, before blood pressure increased, and again after 42 days, when blood pressure was high, and cognitive problems had developed.
At three days, the researchers noticed dramatic changes in the gene expression of three types of brain cells: endothelial cells, interneurons, and oligodendrocytes. Endothelial cells, which line the blood vessels, showed signs of premature aging, including lower energy metabolism and higher senescence markers.
The team also saw early signs of a weakened blood-brain barrier, which normally helps control the movement of nutrients into the brain while blocking harmful substances.
Interneurons, which regulate the balance between excitatory and inhibitory signals in the brain, were damaged, leading to an imbalance similar to what is seen in Alzheimer’s disease.
Additionally, oligodendrocytes, the cells responsible for maintaining the protective myelin sheath around nerve fibers, failed to properly express the genes needed for their maintenance and replacement. This is critical, as neurons depend on healthy myelin to communicate, and without it, cognitive functions begin to decline.
By day 42, when blood pressure had been high for a longer period, more changes in gene expression were observed, coinciding with cognitive decline in the mice.
The researchers were surprised by the extent of the early alterations caused by hypertension.
Dr. Anthony Pacholko, a postdoctoral associate at Weill Cornell and co-lead author of the study, said, “Understanding how hypertension affects the brain at the cellular and molecular levels during the earliest stages of the disease may provide clues for ways to block neurodegeneration.”
One promising step forward is the antihypertensive drug losartan, which is already in clinical use. Losartan blocks the angiotensin receptor and, in experiments, reversed some of the early effects of hypertension on endothelial cells and interneurons in the mouse model.
This suggests that medications designed to treat high blood pressure might also have benefits for cognitive health.
Dr. Iadecola emphasized that treating hypertension remains a priority, as high blood pressure is a leading cause of damage to the heart and kidneys. “Independent of cognitive function, controlling high blood pressure is essential,” he said.
Looking ahead, Dr. Iadecola and his team plan to explore how the premature aging of blood vessels in hypertension might trigger problems in other brain cells like interneurons and oligodendrocytes.
Their goal is to uncover ways to prevent or reverse the effects of hypertension on cognitive function, offering new hope for people with high blood pressure at risk for cognitive decline.
If you care about high blood pressure, please read studies that early time-restricted eating could help improve blood pressure, and natural coconut sugar could help reduce blood pressure and artery stiffness.
For more health information, please see recent studies about added sugar in your diet linked to higher blood pressure, and results showing vitamin D could improve blood pressure in people with diabetes.
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