I AM HDL. HEAR ME ROAR
Dear Diary,
What a day. Things are crazy at work. I have so much to do. It seems that Al’s high blood pressure, his decades of eating poorly, not exercising, being stressed out, and smoking like a chimney, is soon going to catch up with him. The fact that both his mom and his dad died prematurely due to massive myocardial infarctions, not to mention that Al has diabetes and the metabolic syndrome, only make matters worse. He has ALL the major risk factors for atherosclerotic disease.
I spent the last few days just floating around in Al’s blood, surveying the damage. It’s bad. Many of his arteries are coated with fatty streaks of plaque, and consequently are hardening. The man is only 50 and he has plaques everywhere! You should see the ones in his carotid artery! And that one in his left anterior descending coronary artery! Ye Gods! It’s huge! Even I, the smallest of the lipoproteins, could hardly squeeze through. And that plaque looks highly unstable. It’s a ticking time bomb…
What does this all mean to me? Work. And it sure doesn’t help that Al refuses to take medications; he won’t take anything, no statin, no ezetrol, no fibrate, not even niacin or salmon oil. Reckless fool! Me and the other HDLs can only protect him for so long! We need help! If only he would get his cholesterol checked again. The results might scare him into smartening up.
This morning I focused on my main job: removing cholesterol from Al’s peripheral tissues and taking it via his blood to his liver so it can be metabolized. The work never stops. There’s always more! Now I know how postal workers feel. But reverse cholesterol transport is important work, and I play a major role in it. That’s what keeps me going. It’s my raison d’etre. Without lipoproteins like me, the accumulated cholesterol in Al’s blood vessel walls would have caused him to succumb to atherosclerosis many years ago. Another thing I like is that I am part of a team.
I have a great crew. The macrophages, from which I derive Al’s extra-hepatic cholesterol, are really good about presenting their excess cholesterol on their surface so that I can pick it up; they make it easy for my main enzyme, LCAT, to convert that cholesterol into cholesterol esters, which are a form of cholesterol that is easier for me to transport. But the macrophages themselves have help for this process, called cholesterol efflux, and I should give them a nod as well. Hats off to the lipid transporter ABC-A1 and to the receptor SR-B1 for their seminal role in macrophage cholesterol efflux!
Anyway, that was my morning. I spent my afternoon doing a bit of my other jobs, all of which serve to slow the progression of atherosclerosis. In addition to my major role in reverse cholesterol transport, I take pride in my anti-inflammatory, anti-thrombotic, and anti-oxidant properties.
I don’t really know how I do it, but my anti-oxidant properties serve to inhibit the growth of Al’s atherosclerotic plaques. When my infamous cousin, LDL cholesterol, sneaks through the endothelial cell layer lining Al’s arteries and becomes oxidized inside the artery wall, or intima, a cascade of events occurs that results in plaque growth and fatty streaks. This afternoon I slipped inside that nasty plaque in the left anterior descending coronary and managed to prevent some of the LDL from being oxidized by using a few of my enzymes, namely PON1 and LCAT, and my main apolipoprotein, apo-A1. This has got to be one of my favourite parts of my work; I’m at ground zero neutralizing the bad guys. What fun!
This afternoon I also managed to make use of my anti-inflammatory properties. While inside that same plaque, I convinced a couple of cytokines, TNF-α and IL-1, to limit their expression. When these guys get busy, things get ugly. They recruit monocytes to the plaque, which, after differentiating into macrophages, eat the oxidized LDL. Monocytes mean well, but when there’s too many of them the plaque can develop a necrotic core, which gives it its characteristic “gruel-like” appearance, and makes it less stable. I guess monocytes aren’t the sharpest knives in the drawer. Neither are those cytokines I suppose. Idiots. Oh well, it takes all kinds to make the blood go ‘round.
Ah, life is tough. So much cholesterol to transport, so little time. But without me, Al would be a goner.
I am HDL. Hear me roar!