A Heart Attack, Backward — Part 2 of 4: What was in the artery before the clot?

Last week we stopped at the surface of a plaque.

A clot had formed, blood flow had fallen, and the heart muscle downstream was being injured. We followed one common route to a heart attack backward until we reached the artery wall.

Now I want to stay there for a while.

The word plaque is familiar in a dental office. Here it names a different structure: a lesion developing within the artery wall. To understand how it can cause trouble, we need to know what is inside it.

If you missed the beginning, Part 1 starts with the clot.

Blood travels through the lumen, the open channel of the artery. Endothelial cells line its inner surface. Beneath them is tissue in the intima, the innermost layer of the wall. This is where we begin following the plaque.

Cholesterol travels in the blood inside particles, including LDL. Particles containing apolipoprotein B can become retained beneath the endothelium, interacting with molecules in the surrounding tissue.

That retention has experimental support. In a mouse study, LDL engineered to bind less readily to artery-wall proteoglycans produced less atherosclerosis than the comparison LDL. The experiment helps establish the importance of retention. It does not reproduce every step of human coronary disease. Skålén and colleagues, 2002

Once material stays in the wall, the cells around it have something to respond to.

Macrophages can take up lipid and become foam cells, named for their appearance under the microscope. But a foam cell's appearance does not tell you its entire history.

Smooth muscle cells can also accumulate cholesterol and change their behavior. In human coronary arteries obtained from transplanted hearts, researchers found that a substantial share of the foam cells carried smooth-muscle markers. Some also expressed a marker commonly used to identify macrophages. Allahverdian and colleagues, 2014

This matters when we picture the lesion. Cells from the vessel itself are participating, alongside immune cells. The wall is being altered by the behavior of its own inhabitants.

Tissues need to remove dying cells. Other cells engulf them through a process called efferocytosis. That clearance helps prevent the contents from becoming a further source of injury and inflammation.

In advanced plaques, removal can fail to keep up. Dead cells and lipid contribute to a necrotic core: an accumulation of material that the tissue has not successfully cleared.

A study of human atherosclerotic specimens found many more unengulfed apoptotic cells relative to engulfed ones than in the comparison tonsil tissue. The investigators also studied possible causes in laboratory experiments. The human finding supports a failure of clearance; it does not identify one cause operating in every patient's plaque. Schrijvers and colleagues, 2005

This is a useful question to carry into other diseases: what arrived, what was damaged, and what could no longer be removed?

Plaques can contain mineral. There is evidence that cells participate in organizing that mineralization. An early study identified a bone-associated signaling protein in calcified human plaques and observed calcified nodules in cultured artery-wall cells. That work helped establish a biological process worth investigating. Boström and colleagues, 1993

It also makes a simple interpretation of calcium difficult.

In the MESA observational study, greater coronary calcium volume was associated with more cardiovascular events. After accounting for calcium volume, greater calcium density was associated with fewer events. Both findings came from the same analysis. Criqui and colleagues, 2014

That does not make coronary calcium harmless, or tell us that deliberately increasing it would protect someone. It means the quantity and the structure carry different information. A calcium score belongs within a medical assessment, rather than becoming a verdict about a particular plaque from a single number.

We now have retained particles, cholesterol-laden cells, material that has not been cleared, and areas of mineralization. Their arrangement matters, as does the surface separating the lesion from circulating blood.

The artery can also change its shape. Human autopsy work showed that coronary arteries can enlarge as plaque area increases. The amount of disease in the wall and the narrowing of the channel are therefore different measurements. Glagov and colleagues, 1987

Return to last week's clot with that picture in mind. The acute event happened on tissue that had been changing for much longer. Understanding those changes helps explain why looking only at the final obstruction leaves so much of the story out.

For a hygienist, this is part of being able to follow a patient's medical history with more understanding. It does not let us diagnose coronary plaque from an oral examination, and these studies do not establish that periodontal treatment prevents heart attacks. We will examine the oral-systemic evidence in Part 4.

Next week we move to pressure and flow, then to nitric oxide and the oral nitrate pathway. That is where the mouth enters a different part of the circulation story.

— Thad

For the next team huddle: Explain the difference between material within the artery wall and a clot within its channel. Then ask why failed clearance might matter as much as accumulation.

The four-part series:

If this helped, pass it to a hygienist you work with. And reply with the part you would like to look at more closely. Please leave out identifying patient details.