The Molecular Secrets of Atherosclerotic Plaques Revealed by Synchrotron Light
A powerful synchrotron light source can uncover the biochemical secrets hidden within our arteries, revealing clues to preventing heart attacks and strokes.
For decades, doctors have understood that atherosclerosis—the buildup of fatty plaques in arteries—is a leading cause of heart attacks and strokes. What has been less clear is the precise chemical composition of these dangerous plaques and how they change under different conditions. Today, cutting-edge synchrotron technology is allowing scientists to examine atherosclerotic plaques at the molecular level, providing unprecedented insights that could lead to better treatments and prevention strategies.
Why Mouse Models Matter in Cardiovascular Research
To understand human diseases, scientists often rely on animal models that mimic human conditions. In cardiovascular research, the apoE/LDLR-double knockout mouse has become an invaluable tool. These genetically modified mice lack two key genes involved in cholesterol metabolism, causing them to develop severe high cholesterol and atherosclerosis similar to humans, even when fed a normal diet 4 .
When these mice are fed egg-rich diets high in cholesterol, their atherosclerosis accelerates dramatically, making them perfect for studying how diet affects plaque formation and how potential treatments might work 4 7 . The plaques that form in these mice' arteries contain the same key components found in human plaques: lipids, proteins, inflammatory cells, and mineral deposits 4 .
Mouse Model
ApoE/LDLR-double knockout mice develop human-like atherosclerosis, making them ideal for cardiovascular research.
Shining a Light on Plaque Chemistry: The Power of Synchrotron FTIR
Fourier Transform Infrared (FTIR) microspectroscopy is an advanced analytical technique that measures how molecules absorb infrared light, creating a unique "molecular fingerprint" for any biological sample 3 . When this technology is combined with the intense, focused light of a synchrotron radiation source, it becomes powerful enough to reveal detailed biochemical information at the microscopic level 7 .
SR-FTIR Capabilities
- Identify specific biochemical compounds within tiny areas of tissue
- Create detailed maps showing compound distribution
- Detect subtle changes in molecular structure
Synchrotron facilities enable high-resolution analysis of biological samples
A Closer Look at the Groundbreaking Experiment
Research Question and Design
A team of Polish researchers conducted a pivotal study to investigate the biochemical changes occurring in atherosclerotic plaques of apoE/LDLR-double knockout mice under different dietary and treatment conditions 7 . Their goal was to understand how an egg-rich diet affects plaque chemistry and whether the angiotensin-converting enzyme (ACE) inhibitor perindopril—a blood pressure medication—could counter these effects.
1 Standard diet group
Control group for baseline comparison
2 Egg-rich diet group
Pro-atherogenic diet to accelerate plaque formation
3 Egg-rich diet plus perindopril group
Treatment group to test therapeutic effects
After the experimental period, they analyzed the atherosclerotic plaques using SR-FTIR microspectroscopy at the French Synchrotron Facility SOLEIL 7 .
Key Findings: Molecular Changes in Plaques
The SR-FTIR analysis revealed significant biochemical differences between the groups:
Lipid and Protein Content
Mice treated with the egg-rich diet and perindopril showed significantly lower total contents of lipids and proteins in their plaques compared to those receiving the egg-rich diet alone 7 . This suggests that perindopril may help stabilize plaques by reducing the accumulation of these components.
Lipid Saturation Levels
The researchers observed an increase in saturation level of lipids in animals fed the egg-rich diet 7 . Lipid saturation affects how lipids behave in the body and their potential contribution to plaque development. Interestingly, perindopril treatment did not inhibit this effect.
Protein Structure Changes
A significant finding was the change in protein secondary structure in both experimental groups compared to controls 7 . Specifically, the ratio between different protein structures (β-type to α-type) changed, which might affect plaque stability.
Mineral Composition
The egg-rich diet led to higher content of phosphates in the plaques 7 . Phosphates are involved in calcification processes, and increased calcification can make plaques more brittle and prone to rupture.
Spectral Signatures in SR-FTIR Analysis
| Spectral Peak (cm⁻¹) | Biochemical Assignment | Significance in Plaques |
|---|---|---|
| 2850-2950 | Lipids (CH₂, CH₃ stretching) | Indicates lipid accumulation |
| 1656 & 1634 | Proteins (amide I band) | Reveals protein structure changes |
| 1540-1570 | Proteins (amide II band) | Shows protein content |
| 1450-1470 | Lipids (CH₂, CH₃ bending) | Reflects lipid composition |
| 950-1020 | Phosphates (mineral deposits) | Indicates calcification processes |
Research Reagents and Materials
| Reagent/Material | Function in Research |
|---|---|
| ApoE/LDLR-double knockout mice | Genetic model for human-like atherosclerosis |
| Egg-rich diet | Accelerates plaque formation for study |
| Perindopril (ACE inhibitor) | Tests potential therapeutic effects on plaques |
| Synchrotron radiation source | Provides intense IR light for high-resolution analysis |
| Fourier Transform Infrared Spectrometer | Measures molecular vibrations and chemical bonds |
| Paraffin embedding medium | Preserves tissue structure for analysis |
Beyond FTIR: Complementary Advanced Techniques
While SR-FTIR provides detailed chemical information, other synchrotron-based techniques offer additional insights:
Synchrotron radiation-based μCT
Creates three-dimensional images of plaques with exceptional resolution, revealing structural details like thin fibrous caps, lipid cores, and microcalcifications that are invisible to conventional CT scanners 8 . This "virtual histology" allows researchers to study plaques without physically sectioning them.
Elemental Changes in Atherosclerotic Plaques
| Element | Role in Atherosclerosis | Effect of Egg-Rich Diet | Effect of Perindopril Treatment |
|---|---|---|---|
| Calcium | Primary component of calcifications | Increased deposition | Reduced toward normal levels |
| Phosphorus | Partner in calcium phosphates | Increased content | Reduced toward normal levels |
| Zinc | Potential protective effects | Disturbed balance | Restored toward normal balance |
| Iron | Promotes oxidative stress | Increased levels | Counteracted increase |
| Copper | Mixed pro/antioxidant effects | Increased levels | Counteracted increase |
Implications for Human Health and Future Treatments
The findings from SR-FTIR studies provide more than just academic interest—they offer real potential for improving human health. Understanding the precise biochemical changes in atherosclerotic plaques helps researchers:
Develop Targeted Therapies
By identifying specific molecular changes associated with dangerous plaques, drugs can be designed to precisely counter these changes.
Understand Dietary Impacts
The detailed analysis of how egg-rich diets alter plaque composition provides scientific evidence for dietary recommendations.
Repurpose Existing Medications
The positive effects of perindopril found in these studies suggest that certain blood pressure medications might have additional benefits in preventing atherosclerosis progression.
As one research team concluded, these fundamental studies provide crucial insights that inform future clinical research on protecting against atherosclerosis development 4 .
Conclusion: A Brighter Future for Cardiovascular Medicine
The application of synchrotron radiation FTIR microspectroscopy to atherosclerotic plaque analysis represents a perfect marriage of physics and medicine—where powerful light sources from particle physics are harnessed to solve critical medical challenges. As these techniques continue to evolve and become more accessible, they offer hope for deeper understanding of cardiovascular disease and the development of more effective, personalized treatments.
The "molecular fingerprint" of atherosclerosis is becoming increasingly clear, thanks to these advanced technologies that allow us to see the chemical details hidden within our arteries. This knowledge brings us one step closer to defeating a disease that claims millions of lives worldwide each year.