Heart Surgeon:
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Good podcast. I have not assumed that severely damaged arteries would see a meaningful regression or even any regression at all upon lowering lipids. The best we can hope for is stabilization. While both should be lowered if elevated, I’m of the opinion that most people in typical elevated states will realize greater relative benefit from aggressively lowering systemic inflammation with exercise and diet than from lowering particles.
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Yes and no IMO (I am not a cardiologist though). There is a new-ish paper https://www.jacc.org/doi/10.1016/j.jacc.2025.08.047 that spells out the roles of both inflammation and lipoproteins. Both are important. However, it is generally a lot easier to take a pill and lower Apo-B than it is to get people to overhaul their lifestyle of activity and exercise. (And also, starting an exercise program itself can be risky for some people - like if they have a ton of unstable soft plaque, deciding to train for a 5K might actually push you into having an MI. It could be better to stabilise things first rather than aggressively going for exercise.)
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The evidence for inflammation > lipids is meager for lowering CVD event risk.
Anyway, the video is about whether it’s possible to reverse late atherosclerosis to a meaningful extent and the answer is no, lipid lowering instead works in other ways than reversal of disease.
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from a conservative surgeon who has been towing the line for years. I have to agree that at an advanced stage, you need corrective surgery.
but reversing/halting by addressing the issue at an earlier stage is plausible, where a 1% reduction in plaque volume is associated with an 18% reduction in cardiovascular events.
In addition to rouvastatin, I added a tripeptide mixture of GHK-Cu, MT-1, and KPV to my regime. I am not taking afamelanotide (MT-1) to tan; I am using it because of its vascular protective effects.
This actually deserves it’s own page, but go ahead, read it, scrutinize it, share it, discuss:
Afamelanotide (MT-1) functions as a multi-target modulator of arterial health, utilizing melanocortin receptor activation to actively shift the vascular environment from a state of degradation to one of structural resolution.
Macrophage Modulation & Plaque Stability
- Foam Cell Prevention: MT-1 downregulates the CD36 scavenger receptor on macrophages, physically restricting their ability to absorb oxidized LDL (oxLDL) and preventing their transformation into plaque-forming foam cells.
- Reverse Cholesterol Transport: It simultaneously upregulates ABCA1 and ABCG1 transporters, forcing macrophages to pump accumulated cholesterol out of the arterial wall and back onto HDL particles for systemic clearance.
- Structural Remodeling: By altering macrophage behavior, MT-1 reduces the rupture-prone necrotic core of atherosclerotic lesions while increasing stabilizing collagen and smooth muscle content.
IL-10 Upregulation & Immune Resolving
- Direct IL-10 Secretion: MT-1 stimulates macrophages and vascular immune cells to secrete Interleukin-10 (IL-10), a master anti-inflammatory cytokine that actively suppresses destructive immune cascades within the arterial wall.
- NF-κB Suppression: It potently inhibits NF-κB, cutting off the primary genetic switch that drives the release of pro-inflammatory cytokines (such as TNF-α and IL-6) responsible for vascular tissue degradation.
- MMP Inhibition: By dampening these inflammatory pathways, MT-1 acts as an upstream brake against Matrix Metalloproteinases (MMP-2 and MMP-9), the specific enzymes that chew through vascular collagen and elastin.
Angiotensin II (Ang II) & Vascular Tissue Defense
- Nitric Oxide (NO) Bioavailability: MT-1 actively counters the endothelial dysfunction typically driven by Ang II. It enhances eNOS expression and phosphorylation in the vascular lining, ensuring adequate nitric oxide for proper flow-mediated dilation and arterial flexibility.
- Downstream Ang II Interception: While it does not directly crash the renin-angiotensin system (ACE/AT1R) the way an ARB does, MT-1 defends against Ang II by neutralizing its downstream inflammatory damage. It suppresses the oxidative stress and monocyte accumulation that Ang II uses to trigger vascular smooth muscle cell degradation.
- Arterial Compliance: By maintaining endothelial function and halting the inflammatory breakdown of the extracellular matrix, intact melanocortin signaling prevents the increased arterial stiffness and elevated pulse pressure associated with vascular stress.
I think everything in that protocol I posted a few days back could help with plaque regression and general vascular health.
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