Long-term exposure to air pollution raises circulating levels of proprotein convertase subtilisin/kexin type 9 in obese individuals

Abstract

Aims Exposure to airborne particulate matter has been consistently associated with early death and increased morbidity, particularly raising the risk of cardiovascular disease. Obesity, one of the leading cardiovascular disease risk factors, increases susceptibility to the adverse effects of particulate matter exposure. Proprotein convertase subtilisin/kexin type 9 has been related to a large number of cardiovascular risk factors, e.g. atherogenic lipoproteins, arterial stiffness and platelet activation. Thus, the present study was aimed at evaluating, in a series of obese individuals, the effects of particulate matter less than 10 µm in diameter (PM10) on proprotein convertase subtilisin/kexin type 9 circulating levels. Methods and results In 500 obese subjects, participating in the cross-sectional Susceptibility to Particle Health Effects, miRNAs and Exosomes (SPHERE) study, we evaluated the effects of long- and short-term PM10 exposure on circulating proprotein convertase subtilisin/kexin type 9 levels. In the studied individuals (body mass index: 33.3 ± 5.2 kg/m2) with an annual average PM10 exposure of 40.12 ± 4.71 µg/m3, proprotein convertase subtilisin/kexin type 9 levels were 248.7 ± 78.6 ng/mL. In univariate analysis, PM10 exposure (annual average) was associated with proprotein convertase subtilisin/kexin type 9 levels (β=1.83, standard error = 0.75, p = 0.014). Interestingly, in a multivariable linear regression model, this association was observed only for carriers of lower concentrations of interferon-γ, whereas it was lost in the presence of higher interferon-γ levels. Proprotein convertase subtilisin/kexin type 9 levels were positively associated with the Framingham Risk Score, which was raised by 15.8% for each 100 ng/ml rise of proprotein convertase subtilisin/kexin type 9. Conclusions In obese individuals, more sensitive to the damaging effects of environmental air pollution, PM10 exposure positively associates with proprotein convertase subtilisin/kexin type 9 plasma levels especially in those with low levels of interferon-γ.

PCSK9 inhibition and inflammation: A narrative review

“…In the context of an optimal treatment strategy aimed at reducing CV risk, it is useful to identify effects that are specific or shared by either lipid lowering drugs, or anti-inflammatory drugs or a combination of both [139,144]. Moreover, since association studies do not necessarily imply a causal role of PCSK9 in the inflammatory response [145] and data from carriers of loss-of-function mutations in PCSK9, aimed to establish a correlation between plasma inflammation markers and PCSK9 levels are scanty and not conclusive [146,147], evidence Fig. 2.…”

Depression And Cardiovascular Risk – Association Among Beck Depression Inventory, PCSK9 Levels And Insulin Resistance

“…Concerning the relationship between PCSK9 and CV risk, although some studies on PCSK9 levels did not report any association with CV events [38,39], other population studies, meta-analyses and genome-wide association studies have supported the predictivity of PCSK9 levels in CV events [40][41][42]. A genetic reduction of PCSK9 levels by 50% is associated with a similar percent reduction of coronary heart disease (CHD) risk [43] and a genetic large-scale study on 337,536 individuals of British ancestry reported that the rs11591147 loss-of-function PCSK9 mutation had a protective effect not only on hyperlipidemia but also on the risk of CHD (-27%) and ischemic stroke (-39%) [44].…”

PCSK9: A link between air pollution and cardiovascular disease?

“…Moreover, it is important to note that Macchi and colleagues investigated PM 10 as a measure of air pollution only. 9 This partly limits the conclusion of study results regarding the exposure of lower degrees of PM (e.g. PM 2.5 ) and the different compositions of constituents (e.g.…”

“…Further adjustment for potential confounders revealed that this association was limited to obese individuals with lower levels of interferon-g. For short-term exposure to PM 10 , no significant associations were found. 9 PCSK9 binds to the receptor for low-density lipoprotein (LDL) particles and thereby initiates the internalisation of both LDL particles and the LDL receptor into the liver cells. Therapeutically, the blockade of PCSK9 with specific antibodies is paving new avenues in the management of dyslipidemia.…”