Your Arteries are Diseased - THIS is how you Restore them!
Nicolas Verhoeven, PhD
I analyze medical studies to make them understandable & applicable to you
Main Points
Healthy endothelial cells that line the arteries protect against cardiovascular disease by staying in a quiescent, non-proliferative state. This state depends on fat metabolism—especially mitochondrial oxidation of fatty acids via CPT1—which helps produce NADPH, reduce oxidative stress, and suppress inflammation and clotting. When this fat metabolism is impaired, oxidative damage increases. However, acetate, a short-chain fatty acid produced by gut bacteria from dietary fiber or found in fermented foods, can bypass CPT1 and restore these protective effects. Therefore, eating fiber-rich and fermented foods may promote endothelial health by fueling fat metabolism and maintaining the vasculoprotective state critical for long-term cardiovascular health. Dr. Nicolas Verhoeven, PhD / Physionic
Unless you're a manikin, your arteries are very much alive. Far from passive conduits for blood, they are dynamic, responsive tissues—critical to maintaining your health. At the heart of their function are endothelial cells, a thin layer lining the inside of every artery, vein, and capillary in your body. These cells regulate blood pressure, control inflammation, maintain vascular integrity, and manage immune cell traffic. When they’re working properly, they keep your cardiovascular system running smoothly. When they’re not, your risk of plaque buildup, blood clots, strokes, and even death goes up dramatically.
So, what determines whether these cells remain healthy or become dysfunctional? It turns out a big part of the answer comes down to what fuel they burn.
Quiescent vs. Proliferative: The State of Endothelial Health
Endothelial cells can exist in two major states: quiescent, where they are non-proliferative and stable, or proliferative, where they are growing, dividing, and typically responding to stress. Quiescent endothelial cells form a tightly packed, protective barrier along your arteries. This barrier keeps inflammatory cells from infiltrating and blocks other harmful processes like oxidative damage and plaque formation.
However, insults like poor diet, aging, smoking, pollution, or chronic inflammation can stress endothelial cells. Under this stress, they exit quiescence, begin proliferating, and switch their metabolism—shifting from burning fat to primarily using glucose. While this switch is common in many rapidly dividing cells, in the context of endothelial cells, it marks a shift away from protective function and toward vulnerability.
The Metabolic Shift: From Glucose to Fat
Research now confirms that healthy, quiescent endothelial cells upregulate fatty acid β-oxidation—that is, they preferentially burn fat for energy. In contrast, stressed or proliferative endothelial cells shift toward glycolysis, the process of metabolizing glucose. This metabolic identity isn't just incidental—it drives the functional state of the cell.
In experiments comparing endothelial cells in their proliferative vs. quiescent states, glycolysis was found to be elevated in the stressed, dividing cells, while fatty acid oxidation increased significantly in the quiescent ones. Key metabolic enzymes mirrored this shift:
This inverse relationship strongly suggests that the switch to fatty acid metabolism is not just a passive reflection of health but may be a requirement for the quiescent, vasculoprotective state.
Why Does Fat Metabolism Matter So Much?
To understand this, we have to zoom into the mitochondria—the cell's powerhouse. When fatty acids are oxidized, they enter the TCA cycle (also known as the Krebs or citric acid cycle). One of the earliest products of this cycle is citrate, a molecule with crucial downstream functions.
Citrate can be converted into isocitrate, which then feeds into a reaction catalyzed by isocitrate dehydrogenase (IDH). This reaction produces NADPH, a molecule critical to antioxidant defense. NADPH is essential for the function of glutathione reductase, which recharges glutathione, one of the body’s most powerful cellular antioxidants. Without enough NADPH, glutathione cannot neutralize damaging reactive oxygen species (ROS)—unstable molecules that damage DNA, proteins, and lipids.
Indeed, in quiescent endothelial cells, researchers found:
However, when CPT1 was knocked down, blocking fatty acid entry into mitochondria, NADPH levels dropped significantly, and ROS increased. These cells lost their oxidative resilience, showing that fatty acid metabolism is essential for endothelial antioxidant defense.
From Oxidative Stress to Clotting and Inflammation
This shift toward oxidative stress has broad consequences. One of them is the upregulation of PAI-1 (Plasminogen Activator Inhibitor-1), a protein that prevents the breakdown of clots. In endothelial cells exposed to stress (via lipopolysaccharide or LPS), blocking fat metabolism with a CPT1 inhibitor dramatically increased PAI-1 expression—suggesting a move toward a pro-thrombotic state.
The inflammation didn’t stop there. The researchers also found that inhibiting fat oxidation caused an increase in leukocyte adhesion, meaning immune cells were more likely to stick to the endothelial wall—a key step in chronic vascular inflammation and atherosclerosis.
In summary, losing access to fat metabolism:
A Cellular Lifeline: Acetate
So what’s the solution? How can we support endothelial fat metabolism—especially when CPT1 is dysfunctional?
Acetate offers a compelling answer. Acetate is a short-chain fatty acid (SCFA) that, unlike most long-chain fats, does not require CPT1 to enter the mitochondria. It can passively diffuse across the mitochondrial membrane, allowing cells to continue fat oxidation even when CPT1 is impaired.
In experiments where endothelial cells had CPT1 knocked down and were exposed to stress:
These results show that acetate can restore the protective antioxidant and anti-inflammatory effects of fat metabolism, even when the typical fat transport machinery is disabled.
Where Does Acetate Come From?
While our own cells can produce some acetate during metabolism (e.g., from alcohol), the major source of acetate comes from our gut microbiome. When we eat dietary fiber, gut bacteria ferment it into SCFAs—including acetate, propionate, and butyrate. Acetate is then absorbed into the bloodstream, where it can support mitochondrial energy production in tissues like the endothelium.
To increase acetate levels naturally, prioritize:
These fibers are fermented by colonic bacteria into SCFAs that directly fuel your cells. The endothelial cells lining your arteries are primed to absorb and use that acetate—bypassing metabolic roadblocks and restoring redox balance.
A Roadmap to Vascular Health
All of this leads to a powerful conclusion: your metabolic environment shapes your vascular health at the cellular level. When endothelial cells are stressed, they switch to a glycolytic, pro-inflammatory, pro-thrombotic state. When they are quiescent and healthy, they rely on fat—particularly mitochondrial oxidation of long- and short-chain fatty acids like acetate.
Supporting fat metabolism in endothelial cells:
Best of all, this system can be supported naturally—by eating more fiber-rich and fermented foods that boost acetate production. The more you nourish your gut and feed your microbiota, the more they feed you—and your arteries.
Main Points
Healthy endothelial cells that line the arteries protect against cardiovascular disease by staying in a quiescent, non-proliferative state. This state depends on fat metabolism—especially mitochondrial oxidation of fatty acids via CPT1—which helps produce NADPH, reduce oxidative stress, and suppress inflammation and clotting. When this fat metabolism is impaired, oxidative damage increases. However, acetate, a short-chain fatty acid produced by gut bacteria from dietary fiber or found in fermented foods, can bypass CPT1 and restore these protective effects. Therefore, eating fiber-rich and fermented foods may promote endothelial health by fueling fat metabolism and maintaining the vasculoprotective state critical for long-term cardiovascular health.
Dr. Nicolas Verhoeven, PhD / Physionic
References
Reference [Study 490] Kalucka J, Bierhansl L, Vasconcelos Conchinha N, et al. Quiescent endothelial cells upregulate fatty acid β‑oxidation for vasculoprotection via redox homeostasis. Cell Metab. 2018;28(6):881‑894. doi:10.1016/j.cmet.2018.07.016
Funding/Conflicts: Mixed Funding [Public: Research Foundation Flanders (FWO), the Federal Government of Belgium (IUAP7/03), the Flemish Government through Methusalem structural funding, the Swiss National Science Foundation, the British Heart Foundation, the National Natural Science Foundation of China, and several European Union programs including the Marie Curie CIG and ERC Advanced Research Grant (EU-ERC743074). Additional public support came from institutions such as the State Key Laboratory of Ophthalmology (China) and the VIB Tech-Watch Program in Belgium.; Non-Profit: Leopoldina Postdoctoral Scholarship (Germany), the Fritz Thyssen Stiftung, and the Foundation Against Cancer (Belgium). // Potential direct Conflicts of Interest [Peter Carmeliet (P.C.) is named as an inventor on patent applications related to the findings in this paper; All other authors declare no competing interests.]