Lp-PLA2 is an enzyme that operates in the arterial intima and is a marker of vascular inflammation. Higher levels of Lp-PLA2 indicate a doubling of risk for coronary heart disease and stroke. Lp-PLA2 contributes to the formation of vulnerable plaques by promoting inflammation, and its levels can help identify patients who may benefit from more aggressive treatment to lower risk of plaque rupture leading to heart attack or stroke. While methods exist to evaluate plaque composition, measuring Lp-PLA2 provides a non-invasive means to assess risk of cardiovascular events.

1. ROLE OF LIPOPROTEIN
ASSOCIATED PHOSPHOLIPASE A2
in
Atherosclerosis
PRESENTED BY –
SAROJ KUNDAN BHARTI
PHD 1ST YEAR (PHARMACY PRACTICE)
NIPER MOHALI
PRESENTED TO –
Dr. ABHAY H PANDE
Associate Professor, Department of Biotechnology,
NIPER S.A.S. NAGAR

2. Atherosclerosis
It is a disease of large and medium-sized arteries.
Characterized by :-
• Endothelial dysfunction
• Vascular inflammation
• Accumulation of lipids, cholesterol, calcium and cellular debris within the intima
of the vessel wall. [1]
Atherosclerosis can lead to serious problems, including heart attack, stroke or even
death. [2]

3. Atherosclerotic Risk Factors
Atherogenesis is highly complex event and modulated by numerous genetic and
environmental risk factors. [3]
• Genetic
• Degenerative
• Inflammatory
• Cigarette smoking
• Systemic hypertension
• Diabetes mellitus
• Overweight
• Inactivity
• Stress
• Cholesterol problem
Not necessarily cause plaque
Only factor required to cause atherosclerosis

4. Contrasting Histopathological Characteristics of Stable vs Ruptured Plaque

5. Lipoprotein associated Phospholipase-A2
• Lipoprotein-associated phospholipase A2 also known as Lp-PLA2.
• It is a 45-kDa protein with 441 amino acids that is distinct from other members of the
phospholipase A2 family in that it is calcium independent.
• Biologically, it is a vascular-specific proinflammatory enzyme that operates physiologically
in the arterial intima.
• It is a novel biomarker of vascular-specific inflammation.
• Elevated levels of serum Lp-PLA2 are indicative of rupture prone plaque. [5]
• Strong independent predictor of cardiovascular risk, including coronary artery disease, MI,
and stroke.

6. Lp-PLA2 at the Scene of Crime
Staining intensity as lesion progresses Lp-PLA2 strongly expressed within atherosclerotic plaque

7. Stages of plaque development
ATHEROSCLEROSIS PROGRESSES IN A SERIES OF 3 STAGES
Fatty streak development Plaque progression Plaque disruption
Endothelial dysfunction
Lipoprotein entry and
modification
Leucocyte recruitment
Foam cell formation
SMC & leucocyte recruitment.
Evolution of the fatty streak and
calcification.
Fibrous capsule formation.
Luminal Narrowing resulting
claudication or angina
hemodynamic stresses and
degradation of extracellular
matrix.
fibrous cap rupture.
precipitate formation of acute
thrombus which occludes arterial
lumen
acute coronary syndrome

8. Role of Lp-PLA2in the formation of Vulnerable Plaque

9. Currently well-accepted diagnostic tools are available to physicians for assessing cardiovascular risk
like :-
• Framingham and Reynolds risk scoring method.
• Lipid and lipoprotein measurement.
• Carotid ultrasound imaging, stress tests.
• Echocardiography, nuclear imaging.
• Coronary angiography.
• Coronary intravascular ultrasonography.
However, none of these is able to assess whether a patient has vulnerable or rupture-prone plaques.

10. Even though emerging technologies, such as:-
• Virtual histology intravascular ultrasound (IVUS)
• Intravascular ultrasound palpography and thermography
• Optical coherence tomography (OCT)
• Carotid magnetic resonance imaging (CMRI)
may help assess plaque composition and morphologic characteristics, but these approaches
are either invasive or very expensive for widespread utilization. [7]
Thus the ability to measure LP-PLA2 provide critical insights into the active disease and
form clinical strategies to prevent cardiovascular event.

11. Future Aspect
• Tests for other robust biomarkers may be clinically useful in an additive manner.
• For example, it has been shown that while these markers are independent
predictors of risk, Lp-PLA2 added to hs-CRP provides significantly more risk
assessment information over Lp-PLA2 alone. [8]

12. Summary
• Lp-PLA2 is specific for vascular inflammation and is a circulating measure of the
progression of rupture-prone plaque.
• Elevated Lp-PLA2 plasma levels correlate with a doubling of risk for CHD and
stroke in multiple published epidemiological studies.
• Lp-PLA2 levels can be used to identify patients who require more aggressive
treatment, including lipid-lowering therapy.
• Therapeutic intervention can lower Lp-PLA2.

13. References
1. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005 Apr
21;352(16):1685-95.
2. https://www.nhlbi.nih.gov/health-topics/heart-attack.
3. Benjamin, Mina. (2013). Facts and Principles Learned at the 39th Annual Williamsburg Conference
on Heart Disease. Proceedings (Baylor University. Medical Center). 26. 124.
10.1080/08998280.2013.11928935.
4. Stoll G, Bendszus M. Inflammation and atherosclerosis: novel insights into plaque formation and
destabilization. Stroke. 2006 Jul;37(7):1923-32.
5. MacPhee CH, Moores KE, Boyd HF, et al. Lipoprotein-associated phospholipase A2, platelet-
activating factor acetylhydrolase, generates two bioactive products during the oxidation of low-
density lipoprotein: use of a novel inhibitor. Biochem J. 1999 Mar 1;338 ( Pt 2)(Pt 2):479-87.
6. Ballantyne CM, Hoogeveen RC, Bang H, et al. Lipoprotein-associated phospholipase A2, high-
sensitivity C-reactive protein, and risk for incident coronary heart disease in middle-aged men and
women in the Atherosclerosis Risk in Communities (ARIC) study. Circulation. 2004 Feb
24;109(7):837-42.
7. Kolodgie FD, Burke AP, Skorija KS, et al. Lipoprotein-associated phospholipase A2 protein
expression in the natural progression of human coronary atherosclerosis. Arterioscler Thromb Vasc
Biol. 2006;26(11):2523-2529. doi:10.1161/01.ATV.0000244681.72738.bc
8. Melander O, Newton-Cheh C, Almgren P, et al. Novel and conventional biomarkers for prediction of
incident cardiovascular events in the community. JAMA. 2009;302(1):49-57.