Season 1 Episode 9: Atherosclerosis

Most heart attacks don’t start with a clogged artery! They start with a microscopic storm — a small, invisible wound inside the artery wall.

That storm begins decades before symptoms, sometimes before high school. By the time someone hits their forties or fifties, the real question isn’t whether atherosclerosis has begun…It’s how far it’s already gone.

Let’s zoom in — literally inside the artery wall — and trace this disease from its very first spark.
From the moment an ApoB-containing particle sneaks beneath the endothelium…
To the slow, simmering inflammation that follows…
To the day a plaque finally stops being silent.

In this episode of LipidCurious, we’ll uncover 

1. Anatomy & The Birth of an Atherosclerotic Plaque
2. Why Some Arteries Are More Prone to Atherosclerosis
3. Seeing, Treating, and Reversing Atherosclerosis

You’ll walk away seeing cholesterol numbers in a completely different light — not as abstract labs, but as a daily pressure on the artery wall.

By the end, you’ll understand why atherosclerosis is the slow burn beneath the surface — invisible for years, yet capable of erupting into the events we fear most. 

Bonus: For the full collection of visuals across episodes, visit the Podcast page.

Download the Free LipidCurious Starter Kit here

Questions or feedback? Reach out at hello@lipidcurious.com 

Disclaimer: This podcast is for educational purposes only. It is NOT medical advice.

Transcript

SEASON 1 EPISODE 9: Atherosclerosis

Most heart attacks don’t start with a clogged artery.
They start with a microscopic storm — a small, invisible wound inside the artery wall.

And here’s the part no one likes to think about: that storm begins decades before symptoms, sometimes before high school.
By the time someone hits their forties or fifties, the real question isn’t whether atherosclerosis has begun…
It’s how far it’s already gone.

Because by the time we’re reacting to an elevated LDL… or a coronary calcium score… the groundwork has been quietly laid for years.

So today, let’s zoom in — literally inside the artery wall — and trace this disease from its very first spark.
From the moment an ApoB-containing particle sneaks beneath the endothelium…
To the slow, simmering inflammation that follows…
To the day a plaque finally stops being silent.

You’ll walk away seeing cholesterol numbers in a completely different light — not as abstract labs, but as a daily pressure on the artery wall.

Welcome to LipidCurious — the podcast dedicated to demystifying lipids for medical boards and real-world clinical practice.
I’m your host, Dr. Vishnu Priya Pulipati — a board-certified Endocrinologist and Lipidologist.

This is Season 1, Episode 9 — Atherosclerosis — The Slow Burn Beneath the Surface

Here’s what we’ll tackle today:

1. Anatomy & The Birth of an Atherosclerotic Plaque
2. Why Some Arteries Are More Prone to Atherosclerosis
3. Seeing, Treating, and Reversing Atherosclerosis

If you’re new here — welcome!
This entire season builds step by step. For the full picture, I recommend starting at Episode 1.

You’ll find bonus visual handout for everything from Season 1 — plus the free Starter Kit — at www.lipidcurious.com.

And a quick reminder: this podcast is for educational purposes only, not medical advice.

Alright — let’s get started.

Anatomy & The Birth of an Atherosclerotic Plaque

Arteries are like flexible, muscular tubes — lined inside with an extraordinary single, paper-thin layer of cells called the endothelium.
This lining is your body’s non-stick coating — smooth, frictionless, and protective. It keeps blood flowing, prevents clotting, regulates inflammation, and maintains vascular tone.

However, when that endothelial lining becomes inflamed or injured — from years of high ApoB exposure, smoking, hypertension, or high glucose levels — it turns into a sticky Velcro.

This invites ApoB-containing lipoproteins, such as LDL, to slip beneath the surface, which become trapped in the innermost layer of the artery wall, known as the intima.

Now the story heats up.

Inside the wall, LDL wanders into a rough neighborhood full of free radicals — unstable molecules missing an electron and eager to steal one. 

Free radicals are produced naturally as part of cellular metabolism, but smoking, air pollution, and chronic inflammation significantly increase their numbers.
 And when they find LDL nearby — bam! — they snatch an electron, damaging it. Our once-innocent LDL becomes oxidized LDL — the real troublemaker in this story.

Oxidation isn’t a single event.  It’s fueled by free radicals, by enzymes like myeloperoxidase and lipoxygenase, by heavy metals like iron and copper, by autoantibodies, and by plain old inflammation.
Oxidation is a biochemical process that transforms LDL from a helper to a hazard.

Once oxidized, LDL goes rogue — and it wreaks havoc in four significant ways:

1.    Injures the endothelium

2.    Creates foam cells

3.    Stimulates smooth muscle migration and proliferation

4.    Activates platelets

Here’s how that unfolds:

The injured endothelium sends out distress signals — adhesion molecules.
Monocytes respond, slip inside, and transform into macrophages.

Macrophages start swallowing oxLDL through scavenger receptors, swell up, and become foam cells — tiny fat-filled bubbles.
Clusters of foam cells form fatty streaks, the earliest visible sign of atherosclerosis.
And yes — we see them in teenagers.

Now they have become a part of the problem. Good intention; bad outcome.

Foam cells don’t sit quietly.
They release inflammatory cytokines, reactive oxygen species — calling in more immune cells and worsening the storm.
Some foam cells die, dumping lipid debris into the wall, creating the necrotic core of a plaque.

Meanwhile, smooth muscle cells — normally structural and calm — get lured from media (middle layer) into the intima.
They multiply, lay down collagen, and try to “patch” the area.
This creates the fibrous cap — strong enough to cover the plaque, fragile enough to rupture. 

As foam cells, lipids, and collagen build, the artery stiffens and remodels.

And oxLDL keeps activating platelets, priming the wall for atherothrombosis — the clot that turns quiet disease into a heart attack.

A plaque isn’t a static clog.

It’s living, dynamic tissue — stabilizing, growing, or destabilizing depending on the daily tug-of-war between injury and repair.

When someone says, “My blockage happened overnight,”

What really happened was decades of quiet remodeling that finally tipped over.

Atherosclerosis is a slow, smoldering volcano.

You don’t notice it until it erupts.

Why Some Arteries Are More Prone to Atherosclerosis

So why do two patients with the same LDL walk out with completely different futures?
One has a pristine CTA.
The other is scheduling a stent.

Same cholesterol. Different destiny.

First: genetics.
Some people inherit higher ApoB particle counts or elevated Lp(a) 
Even “normal” cholesterol hits harder in these arteries.

Second: inflammation.
Diabetes, obesity, smoking, hypertension — all make the endothelium leaky and irritable.
One person has a smooth, resilient surface; the other has Velcro.

Third: blood flow.
Plaques form at bends, curves, and branch points where shear stress is low — the quiet eddies of a river.

Put these together — genetics, chronic inflammation, and turbulent flow — and you start to see why one patient builds plaque like concrete and another barely forms a streak.

And it explains why people with “great numbers” sometimes end up in the cath lab…
while others with modest elevations never do.

Because atherosclerosis isn’t just about how high LDL is.
It’s about how long the artery has been exposed to ApoB — and how reactive that vessel wall is to that exposure.

This is where CAC scoring and plaque imaging shine — they measure actual disease, not just risk factors.

Cholesterol lights the match.
Genetics, inflammation, vessel biology, and time decide how fast the fire spreads… and where it burns first.

Seeing, Treating, and Reversing Atherosclerosis

Here’s where things finally turn hopeful.
Once you can see atherosclerosis, you can target it precisely.

Let’s start by understanding the different types of plaques.

Stable plaques build up slowly over time. They harden the artery wall and are much less likely to rupture.

Vulnerable, or rupture-prone, plaques are the real troublemakers — large, soft lipid-rich cores covered by thin, inflamed caps. They’re almost like a fat-filled blister sitting under tension, just waiting to pop. They make up only 10–20% of all plaques… yet they cause 80–90% of acute events.

And then we have complicated or erosion-prone plaques. These don’t rupture; instead, the fibrous cap stays intact, but the surface layer — the endothelial cells — erodes. That superficial erosion sparks clot formation right on top of the plaque, leading to the same downstream danger: thrombosis.

We look at plaque through two lenses: non-invasiveand invasive imaging.

Non-invasive first:

Calcium scoring: great for asymptomatic, intermediate-risk adults. But a zero score in symptomatic patients? Not reassuring. That’s the Zero Calcium Paradox. Coronary CTA, MRA, PET/CT can detect soft plaque, inflammation, and remodeling. Carotid ultrasound and ABI offer systemic clues.

Invasive imaging:

Optical Coherence Tomography gives near-microscopic detail: fibrous cap thickness, lipid pools, macrophage clusters.

Intravascular Ultrasound (IVUS) with Near-Infrared Spectroscopy (NIRS) shows plaque structure and chemical composition, especially its lipid content.

These aren’t just diagnostic toys — they’re windows into the biology of the artery wall.

Here’s the good news: the biology is modifiable.

• Statins: stabilize plaques, thicken caps, reduce inflammation, increase dense calcium (so CAC looks worse, but plaque is safer).
• Ezetimibe: reduces plaque volume, thickens caps.
• PCSK9 inhibitors: regress lipid-rich plaque and cool inflammation.
• Inclisiran, bempedoic acid: reduce inflammation and stabilize plaque.
• Fibrates: reduce thrombogenicity.
• Omega-3s: stabilize plaques and reduce inflammatory cytokines.
• GLP-1 RAs and SGLT2 inhibitors: improve metabolic tone and endothelial health.

Can we reverse atherosclerosis?

Partially — biologically, not geometrically.

Regression means:

• lipid core shrinks
• fibrous cap thickens
• inflammation cools
• plaque becomes quiet

You’ve turned an active volcano into a dormant one.

That’s success.

And this is why lipid management isn’t about chasing a number — it’s about changing the biology of the arterial wall.

If everyone could see their disease, we’d treat risk far earlier, with far more purpose.

Take-Home Points

1. Atherosclerosis begins early and silently — long before symptoms.
2. Imaging reveals plaque biology that LDL alone can’t.
3. Lowering ApoB and inflammation stabilizes — and can regress — plaque.

Alright folks, our next episode drops in two weeks — we’ll be wrapping up season 1

Thanks for tuning in to LipidCurious.

I’m genuinely thankful for all the encouragement and feedback — it’s been incredibly uplifting. 
If today’s episode was helpful, share it with a friend or colleague.
I’d love to hear your feedback or topic suggestions — you can always reach me at hello@lipidcurious.com.

Be sure to subscribe or follow so you don’t miss what’s next.
 And don’t forget — you can grab the free Starter Kit and Season 1 Visual Guide at www.lipidcurious.com.

Until next time — stay curious, and stay confident.
Signing off, Dr. Pulipati.

Bonus: For the full collection of visuals across episodes, visit the Podcast page.

Download the Free LipidCurious Starter Kit here

Questions or feedback? Reach out at hello@lipidcurious.com