APOA2

The need for an advanced understanding of lipidology structure and function in healthcare is growing.   Lipoprotein testing provides valuable insights into an individual's lipid profile, aiding in the assessment of cardiovascular risk and guiding interventions above and beyond the standard lipid panel.  

Apolipoprotein A1 (ApoA1) and apolipoprotein A2 (ApoA2) are two distinct proteins that play essential roles in lipid metabolism and cardiovascular health. While both are constituents of high-density lipoprotein (HDL) particles, they differ in their structural characteristics and functions. 

ApoA1 is the major protein component of HDL particles and is primarily involved in the formation and stabilization of HDL  as well as facilitating the reverse cholesterol transport pathway, which removes excess cholesterol from peripheral tissues and transports it back to the liver for excretion.

In contrast, clinical and epidemiological studies have yielded conflicting results regarding the role of apoA-II in cardiovascular health, with human apoA-II deficiency showing minimal impact on lipoprotein levels and limited clinical consequences. 

Elevated plasma apoA2 concentrations have been linked to hypertriglyceridemia and reduced HDL levels in humans, leading to dyslipidemia and glucose intolerance. This dysregulation in lipid and glucose metabolism may contribute to the development of type 2 diabetes (T2D), creating a potential feedback loop.  [7.]

In this article, we delve into the intricacies of ApoA2, exploring its function, clinical significance, testing options, interpretation of results, and natural strategies to optimize its levels through dietary, lifestyle, and supplement interventions. Additionally, we provide insights into the ApoA2 test, its procedures, and its importance in assessing cardiovascular risk.

Understanding ApoA2

What is ApoA2?

Lipoproteins are soluble proteins that can transport lipids throughout the body.

Apolipoprotein A2 (ApoA2) is a lipoprotein synthesized mainly in the liver and also in the small intestine.  [7.]

HDL molecules are composed of a shell of phospholipids and unesterified cholesterol along with a distribution of lipoproteins and a center of cholesterol esters and triglycerides.  

ApoA2 is a secondary apolipoprotein component of some high-density lipoprotein (HDL) particles, with apolipoprotein A1 being the dominant lipoprotein on all HDL particles.  Two types of HDL particles may be present in humans: those containing only ApoA1 lipoproteins, and those containing both ApoA1 and ApoA2 lipoproteins.  [7.]

Functions of ApoA2: What Does ApoA2 Do?

ApoA2 is still not very well understood.  It seems that HDL particles containing both ApoA1 and ApoA2 subfractions are involved in lipid transport, while those containing only ApoA1 lipoproteins are involved in hemostasis, immune response, and reducing the inflammatory response.  [7.]

Conflicting data exist regarding the function of HDL particles containing both ApoA1 and ApoA2; earlier studies demonstrated that HDL particles containing only ApoA1 were more efficient at reverse cholesterol transport than those containing both ApoA1 and ApoA2, while newer data suggests that the presence of ApoA2 may stimulate additional cholesterol efflux pathways and aid in reverse cholesterol transport.  [7.]

Clinical Significance of ApoA2

The clinical significance of ApoA2 levels on lipid metabolism and cardiovascular health is still being elucidated.  

ApoA2 and Cardiovascular Health

In humans with a primarily lipid abnormality of low HDL levels, therapy with gemfibrozil to increase the expression of ApoA1 and ApoA2 was associated with a reduced incidence of coronary artery disease events.  [7., 17.]

However, the current consensus points to an association with increased risk of atherogenesis with HDL particles containing both ApoA1 and ApoA2.  [7., 11.]

The CARDIA study demonstrated that ApoA1 and ApoA2 lipoproteins may be present in humans in a variety or proteoforms, or shapes, and that different proteoforms may correspond to different health outcomes.  [20.]  This finding may highlight the reason for diverse findings in previous studies regarding the effects of ApoA2 lipoproteins on lipid metabolism.  

ApoA2 and Metabolic Syndrome

In the setting of diabetes, increased inflammation is present.  This chronically increased inflammation causes ApoA2 proteins to undergo structural changes by oxidizing the ApoA2 lipoprotein at key locations.  This makes the HDL particle more hydrophilic, and reduces its capacity for cholesterol efflux.  [1.]

ApoA2, Immunity, and Amyloidosis

HDL particles have demonstrated antiviral activity in response to acute infections including COVID-19, although this effect was lost upon glycation.  [5.]  ApoA2 lipoproteins have also demonstrated immunomodulatory and immune-stimulating effects.  [5., 10., 19.]

Certain apoA2 isoforms and altered ApoA2 levels may also be an early marker for cancer.  [7.] 

Finally, a link between ApoA2 and amyloidosis has been demonstrated.  [7.]

Summary of the Clinical Significance of ApoA2  [7.] 

While it is still difficult to elucidate the exact meaning of ApoA2, it can provide important clinical information within the context of an individual’s overall health history and cardiovascular disease risk profile.  

Understanding ApoA2 levels along with ApoA1 levels, HDL particles, ApoB levels, and other markers of cardiometabolic health may provide the most comprehensive understanding.  Also, as we learn more about the significance of ApoA2 isoforms on human health, this may also become an important clinical indicator of health or disease.  

ApoA2 is the second most abundant protein in HDL particles.  It plays a crucial role in lipid metabolism and cardiovascular health, though its precise functions remain controversial in the literature. 

Recent mass spectrometry proteomics studies have emphasized the significance of subtle modifications of ApoA2 associated with different phenotypes, highlighting the importance of characterizing specific isoforms rather than overall levels. 

ApoA2 has been implicated in dyslipidemia and in diseases beyond lipid metabolism, including amyloidosis.  Furthermore, ApoA2 alterations have been identified as potential biomarkers for various cancers, particularly pancreatic cancer, underscoring its importance in early diagnosis. 

Despite extensive research, further investigation is needed to fully elucidate the multifaceted roles of ApoA2 in human health and disease.

ApoA2 Testing Options

Overview of ApoA2 Testing

ApoA2 testing involves assessing the levels of apolipoprotein A2 (ApoA2) in the bloodstream, typically through blood serum or plasma samples.  Venipuncture is commonly required.

ApoA2 genetic sequencing is also ordered, and typically requires a whole blood sample.  

Preparation and Procedure for ApoA2 Testing

Preparation for ApoA2 testing typically involves fasting for 8 to 12 hours before blood collection to ensure accurate results. Blood samples are collected via venipuncture and processed to separate serum or plasma.  They are then sent to a lab for analysis.

Natural Ways to Optimize ApoA2 Levels

Diet and lifestyle provide important tools to optimize lipid levels, including HDL cholesterol and its associated lipoproteins.  

Dietary Strategies

Diets Containing Fermented Dairy Products: diets containing fermented dairy products have been shown to increase ApoA1 levels.  [9., 14.]  

Foods Rich in Omega-3 Fatty Acids: Fatty fish (salmon, mackerel, sardines), flaxseeds, chia seeds, walnuts all have scientific evidence of efficacy in increasing ApoA1 levels and reducing cardiovascular disease risk.  [9., 14.]

Fiber-Rich Foods: Whole grains (oats, barley, quinoa), fruits (apples, berries, oranges), vegetables (broccoli, Brussels sprouts, carrots), legumes (beans, lentils) are all Mediterranean diet staples that have shown effectiveness in raising ApoA1 levels and reducing cardiovascular disease risk.  [14.]

Avoid excess sugar: diets high in sugar are highly negatively correlated with ApoA1 levels.  [9.]

Lifestyle Modifications

Regular Exercise: Aerobic activities (walking, jogging, swimming), strength training, yoga, tai chi may all benefit ApoA1 levels and promote cardiovascular health.  [9., 21.]

Smoking Cessation: Quitting smoking reduces oxidative stress and inflammation, contributing to improved lipid profiles.  [9.]

Stress Management: Techniques such as meditation, deep breathing exercises, yoga, and mindfulness may help lower stress levels and improve overall cardiovascular health,and in some cases may also have a positive effect on lipid profiles.  [16.]

Niacin (Vitamin B3): Niacin supplementation has been shown to improve HDL cholesterol levels.  [4.]