From the Guidelines
Phospholipase A2 (PLA2) is a proatherogenic enzyme associated with an increased risk of cardiovascular disease (CVD) and stroke. The clinical significance of PLA2 is evident in its ability to hydrolyze oxidized phospholipids in LDL, leading to the generation of lysophosphatidylcholine, oxidized nonesterified fatty acids, and other active phospholipids and inflammatory mediators 1.
Key Points
- Association with CVD risk: PLA2 has been associated with an adjusted OR for CVD of 1.60 (95% CI 1.36 to 1.89) in a meta-analysis of 14 studies 1.
- Risk prediction: PLA2 mass and activity have been shown to improve risk discrimination over and above models accounting for standard risk factors, although the increments are small 1.
- Stroke risk: Several studies suggest a relationship between PLA2 and stroke risk, with high-sensitivity C-reactive protein (hs-CRP) being the most commonly used marker 1.
- Inflammatory conditions: PLA2 has been linked to inflammatory conditions such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), which are associated with an increased risk of CVD and stroke 1.
Clinical Implications
The clinical significance of PLA2 highlights the importance of considering inflammatory markers in the assessment of CVD and stroke risk. While the use of PLA2 inhibitors, such as varespladib, has been explored, further research is needed to determine their therapeutic benefits. Additionally, medications like anakinra, an interleukin-1 receptor antagonist, have been investigated for their ability to reduce PLA2 activity. However, the clinical implications of these findings are still being studied, and more research is needed to fully understand the role of PLA2 in CVD and stroke prevention.
From the Research
Clinical Significance of Phospholipase A2 (PLA2)
The clinical significance of Phospholipase A2 (PLA2) is evident in its role in various pathological conditions, including:
- Inflammatory diseases, such as arthritis and atherosclerosis 2, 3
- Cardiovascular diseases, including atherosclerosis and aneurysm formation 4, 5
- Neurological diseases and cancer 5
- Snake venom toxicity, where PLA2 activity is a key component of venom toxicity 6
Therapeutic Potential of PLA2 Inhibitors
The therapeutic potential of PLA2 inhibitors is being explored in various clinical trials, including:
- Treatment of atherosclerosis and aneurysm formation, where inhibitors such as varespladib have shown promise 4
- Treatment of inflammatory diseases, such as psoriasis and atopic dermatitis, where cytosolic PLA2 inhibitors are being tested 5
- Treatment of snakebite, where broad-spectrum PLA2 inhibitors such as varespladib may offer a potential therapeutic option 6
Challenges and Limitations
Despite the potential of PLA2 inhibitors, there are challenges and limitations to their development, including:
- The complex nature of PLA2 enzymes and their multiple forms, which can make it difficult to design specific inhibitors 3
- The lack of understanding of the relevant PLA2 enzyme that regulates arachidonic acid release and eicosanoid biosynthesis 3
- The failure of some PLA2 inhibitors, such as darapladib and varespladib, to reach the market or show efficacy in clinical trials 5