Thread by @KatiOorni

Did you know that atherosclerotic lesions are acidic?
(1/15)

rdcu.be/bRXph

Extracellular acidity in atherosclerosis is one of my favorite topics, so I'm really, really excited about this study (2/15)

The authors show that some individuals have carotid atherosclerotic lesions that have an acidic pH. They show this is due to activation of Na+-H+ exchanger in macrophages, which leads to extrusion of H+ and extracellular acidification (3/15)
rdcu.be/bRXph

Acidic extracellular pH has been reported also earlier. Naghavi and co-workers promoted the idea that plaques having an acidic extracellular pH might be rupture-prone (4/15)

ncbi.nlm.nih.gov/pubmed/12119190

One reason for the acidity may be that atherosclerotic plaques are also hypoxic (5/15)

sciencedirect.com/science/articl…

The blue colour in the figure shows hypoxic areas

But that's not the whole story. Lesional macrophages need a lot of energy and glycolysis is much much faster way to produce ATP than oxidative phosphorylation. Aerobic glycolysis is called the Warburg effect and it's been studied a lot in cancer (6/15)

Whether glycolysis happens in hypoxia or normoxia, it leads to generation of lactate and H+, which are secreted. This then leads to extracellular acidification. (7/15)

So what? (8/15)

Well, actually, acidic extracellular pH seems to aggravate almost everything that happens with #LDL and #macrophages in atherosclerosis and worsen #HDL functions (9/15)

We wrote a review about this a couple of year ago (10/15)

Acidification of the intimal fluid: the perfect storm for atherogenesis ncbi.nlm.nih.gov/pmc/articles/P…

At acidic pH LDL retention and modification are increased, LDL aggregation and cholesterol crystallization are increased, foam cell formation is increased. So all the processes that increase accumulation of LDL-derived lipids in the arterial wall seem to be increased (11/15)

To make make matters worse, reverse cholesterol transport (RCT) by HDL becomes weaker. The expression of receptors involved in RCT are downregulated and HDL is modified to make it a weak cholesterol acceptor. So, removal of cholesterol from the arteries is decreased (12/15)

Oh and one more thing. Inflammatory responses in the arterial wall are increased at acidic pH. This includes #inflammasome activation (13/15)

So. Getting back to the study by Liu and coworkers (rdcu.be/bRXph). They had nice methods to show acidic atherosclerotic areas in frozen tissue sections, ex vivo sampes and in live mice (14/15).

It'll be interesting to see what happens next with the new tools to visualize the acidic areas in the arterial wall. But in the meantime, keep in mind that atherosclerotic lesions are acidic and that makes everything so much worse (15/15).