Aims
Atherogenesis is dependent upon monocyte influx into the vessel wall. In humans, three monocyte subsets exist, the number and function of which are significantly altered in cardiovascular disease (CVD). Whether such alterations arise in individuals with a perturbed lipid profile remains largely unanswered, but is important to delineate, as adoption of a pro-inflammatory state may promote plaque formation. Here, we compared the inflammatory status of monocyte subsets and determined whether monocyte inflammatory changes are evident in individuals with a perturbed lipid profile.
Background and aims
Atherogenesis is dependent upon monocyte influx into the vessel wall. In humans, three monocyte subsets exist, the number and function of which are significantly altered in cardiovascular disease (CVD). Whether such alterations arise in individuals with a perturbed lipid profile remains largely unanswered, but is important to delineate, as adoption of a pro-inflammatory state may promote plaque formation. Here, we compared the inflammatory status of monocyte subsets and determined whether monocyte inflammatory changes are evident in individuals with a perturbed lipid profile.
Conclusions
Our data indicates that priming of all monocytes to an inflammatory state occurs in individuals with a perturbed lipid profile, overriding the normal functional distinction attributed to the different monocyte subsets. As such, all monocytes may be important in CVD.
Methods
Monocyte subset cytokine production, inflammatory and anti-inflammatory marker expression were determined by whole blood flow cytometry and related to participants' lipid levels.
Results
The intermediate and non-classical monocytes were more inflammatory than classicals as seen by their higher cytokine production (TNF-α, IL-1β, IL-6) and M1 marker (CD86) expression, but lower levels of M2 markers (CD93, CD163). More importantly, a considerable variation was seen between participants, with all monocytes of one individual being more inflammatory than those of another. Many inter-individual differences were related to participants' lipid levels. IL-1β production correlated negatively with Apo A1 and HDL-C. CD86 and TLR2 correlated positively with Chol:HDL-C but negatively with HDL-C and Apo A1:Apo B. Interestingly, CD163 expression correlated positively with Chol:HDL-C but negatively with Apo A1:Apo B. Conclusions: Our data indicates that priming of all monocytes to an inflammatory state occurs in individuals with a perturbed lipid profile, overriding the normal functional distinction attributed to the different monocyte subsets. As such, all monocytes may be important in CVD.