The heart has its lesions

Crystallizing cholesterol has a starring role to play in causing cardiac damage

Plague builds up on the walls of arteries.

Plague builds up on the walls of arteries. Dr Abela argues expanding crystals of cholesterol push out bits that can block the artery. Image: Wikimedia/CC 4.0

George Abela had always pointed out to a link between cholesterol crystals and heart attacks. But according to recent research his team now have a better idea why, when and how that happens.

Abela, a cardiologist at Michigan State University, and his team learned that what it takes is a high concentration of cholesterol in the blood, a drop of a few degrees in ambient temperature, more alkaline blood, the conversion of cholesterol molecule into cholesterol monohydrate or a combination of these factors.

Now cholesterol monohydrate crystals, which may look like needles or plates, have been found in the plaque tissue seen in atherosclerosis (the build-up of bodily gunk of fat, calcium, cholesterol that can narrow arteries, somewhat akin to the buildup in old plumbing), arterial smooth muscles, even in eye cells.

To convert cholesterol monohydrate back into the more benign cholesterol calls for temperatures up to 86 degrees C (or187 degrees F), admittedly a temperature rather unusual to be found in a heart of a living human.

Dr. George Abela

While explaining his research a few years ago, Abela had described how the “flow of sharp-ended crystals in arteries damage the lining of arteries and decrease the ability of arteries to dilate properly at intervals far away from the site of the attack.”

In a press release that MSU put out after his most recent work, he said, “In previous studies, we showed that when cholesterol goes from a liquid to a solid, or crystal state, it expands in volume like ice and water. This expansion inside the wall of the artery can tear it and block blood flow causing a heart attack or stroke.”

These crystals are released from plaque that can build up in the heart and is often made up of fat, calcium, cellular waste (often from broken down foam cells, the product of immune cells that fight cholesterol, cholesterol itself and other material. That thickening lining is what is called atherosclerosis. Just as sufficient thickening could block the vessels, so can bits breaking off and plugging up the works. And Abela’s work that expanding bits of crystallizing cholesterol can push bits of the plaque out and block blood flow to the heart causing tissue and death there (that is, a heart attack) opens new doors.

Of 286 patients, the team found that 240 had cholesterol (monohydrate) crystals packed in to recognizable clusters with totally blocked arteries having predictably larger clusters than partially occluded ones.

The spiky bits are cholesterol crystals that tear and damage the artery wall

The spiky bits are cholesterol crystals that tear and damage the artery wall

Besides expanding and tossing in stuff that clogs up the waterworks, cholesterol crystals also spurs large white blood cells called macrophages to switch on a gene called NLRP3, which produces a protein called cryopyrin, which causes local inflammation. The presence of cryopyrin in the blood, Abela argued, could be good predictor of who would be clutching their chests and falling to the floor – though not quite in those terms.

If cholesterol can no longer move in mysterious ways its blunders to perform, there are possible ways to fix the damage it wreaks.

“Now that we’ve shown how extensive cholesterol crystals are irritating and blocking off these arteries, treatments that dissolve these crystals may be used to reduce heart damage,” Abela said.

The team studied the effects of statins (standard treatment for lowering cholesterol) on cholesterol crystals in a test tube. Statins dissolved the crystals, and in a dose-dependent way. Now at least one pharmaceutical is taking things further to try and show that one statin, canakinumab, which blocks the Interleukin-1 beta inflammation molecule, can reduce the chances of a cardiac mishap.

“Saving heart muscle is the most important aspect of treating a heart attack,” Abela said. “So, if we are able to provide patients with better, more targeted treatments, then this could help open up and calm down the aggravated artery and protect the heart muscle from injury.”
The team’s research was published in the August 2017 edition of the American Journal of Cardiology.

Below is a 2013 video describing the formation of cholesterol crystals: