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This week, we're exploring a condition that affects 40% of middle-aged adults and nearly 75% of those over 60: atherosclerosis.
Most people think of atherosclerosis as plaque simply "clogging" the arteries. But these plaques are surprisingly active, and can even grow their own blood vessels.
This process, known as intraplaque angiogenesis, is an emerging focus in cardiovascular research.
Atherosclerosis: More Than just Fats
Atherosclerosis begins when the endothelium — the thin inner lining of blood vessels — becomes damaged by factors such as high blood pressure, smoking, elevated blood sugar, or excess circulating lipids.
This damage makes the vessel wall more permeable, allowing LDL cholesterol particles to move beneath the endothelial surface and accumulate within the artery wall.
In response, immune cells called monocytes enter the vessel wall and transform into macrophages. These cells attempt to clear excess lipids but can become overloaded, forming foam cells that drive chronic inflammation inside the plaque.
As inflammation persists:
Smooth muscle cells migrate into the plaque
Fibrous tissue begins to form
The artery wall thickens and stiffens
→ Over time, plaques can narrow blood flow and destabilize the vessel itself.
Intraplaque Angiogenesis: When Plaques Grow Their Own Blood Vessels
As plaques enlarge, oxygen delivery inside the plaque becomes limited. Cells respond by releasing VEGF and other signals that stimulate new blood vessel growth.
This process is called intraplaque angiogenesis.
Tiny microvessels begin growing into the plaque from the vasa vasorum — the small vessels that normally supply the outer artery wall.
But these newly formed vessels are often abnormal:
Thin and poorly supported
Disorganized
Highly permeable
As a result, red blood cells, inflammatory immune cells, and lipids can leak directly into the plaque.
This leakage can increase oxidative stress and inflammation, expand the plaque core, and weaken the fibrous cap that stabilizes the plaque
→ These changes are strongly associated with plaque instability, rupture, and cardiovascular events such as heart attack and stroke.
Why are newly formed blood vessels inside atherosclerotic plaques considered dangerous?
A Double-Edged Process
Angiogenesis in atherosclerosis is complex. In some contexts, it may support tissue repair and blood flow. While in others, it contributes to disease progression and risk. The impact depends on the balance between stable and abnormal vessel growth.
Emerging Research Directions
Current research is focusing on plaque behavior and vascular instability, specifically how abnormal microvessels contribute to plaque progression and rupture.
Current investigations include:
They found that plaques with higher expression of angiogenesis-related genes also showed greater immune cell activity, suggesting that abnormal vessel growth and inflammation may work together to drive plaque progression and rupture. The study also developed a machine learning model capable of predicting intraplaque hemorrhage risk based on angiogenesis-related gene expression.
They found that inhibiting bFGF signaling reduced intraplaque angiogenesis, intraplaque hemorrhage, and macrophage infiltration without impairing normal vessel structure. Mechanistically, bFGF lowered VCAM-1 and CCL2 expression, molecules that help recruit inflammatory immune cells into plaques.
In ApoE knockout mice, EPO increased proteins involved in hypoxia signaling, inflammation, and new blood vessel formation. They observed activation of the PI3K/AKT/mTOR pathway, which helps regulate endothelial cell growth and survival. Importantly, plaques exposed to EPO showed higher rates of intraplaque hemorrhage, suggesting that excessive angiogenic signaling may contribute to formation of fragile, leaky microvessels within vulnerable plaques.
Don't miss this week's recipe featuring sardines, kale, and pine nuts —ingredients rich in omega-3 fats, fiber, and polyphenols that support cardiovascular health and healthy inflammatory balance.
Check out this weeks youtube video to see our mascot Dr. Angio bringing complex health and research topics to life.
Best wishes,
- The Angiogenesis Foundation
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