Intra-city Differences in Cardiac Expression of Inflammatory Genes and Inflammasomes in Young Urbanites: A Pilot Study

Abstract

Southwest Mexico City (SWMC) air pollution is characterized by high concentrations of ozone and particulate matter < 10 μm (PM(10)) containing lipopolysaccharides while in the North PM(2.5) is high. These intra-city differences are likely accounting for higher CD14 and IL-1β in SWMC v NMC mice myocardial expression. This pilot study was designed to investigate whether similar intra-city differences exist in the levels of myocardial inflammatory genes in young people. Inflammatory mediator genes and inflammasome arrays were measured in right and left autopsy ventricles of 6 southwest/15 north (18.5 ± 2.6 years) MC residents after fatal sudden accidental deaths. There was a significant S v N right ventricle up-regulation of IL-1β (p=0.008), TNF-α (p=0.001), IL-10 (p=0.001), and CD14 (p=0.002), and a left ventricle difference in TNF-α (p=0.007), and IL-10 (p=0.02). SW right ventricles had significant up-regulation of NLRC1, NLRP3 and of 29/84 inflammasome genes, including NOD factors and caspases. There was significant degranulation of mast cells both in myocardium and epicardial nerve fibers. Differential expression of key inflammatory myocardial genes and inflammasomes are influenced by the location of residence. Myocardial inflammation and inflammasome activation in young hearts is a plausible pathway of heart injury in urbanites and adverse effects on the cardiovascular system are expected.

Keywords: cardiovascular risk factor; children; inflammasomes; mast cells; myocardial inflammation; particulate matter; urban pollution.

Fig. 1.

A: Trends of annual averages, maxima and 90^th percentiles of 24-hr PM_2.5 levels in the North Mexico City Tlalnepantla (NMC) monitoring station for the period 1997–2010. The levels for the period 1997–2003 were estimated from PM₁₀ data using a regression equation (R² = 0.71) for simultaneous PM₁₀ and PM_2.5 data registered between 2003 and 2007 at the same site. PM data were obtained from the Secretaría del Medio Ambiente, Gobierno del Distrito Federal (SMA-GDF, 2011). B: Trends of annual averages, maxima and 90^th percentiles of 24-hr PM_2.5 levels in the Mexico City Southwest Pedregal monitoring station for the period 1997–2010. The levels for the period 1997–2003 were estimated from PM₁₀ data using a regression equation (R² = 0.65) for simultaneous PM₁₀ and PM_2.5 data registered between 2003 and 2007 in the same site. PM data were obtained from the Secretaría del Medio Ambiente, Gobierno del Distrito Federal (SMA-GDF, 2011).

Fig. 2.

A: Left ventricle in a 14 year old NMC boy. There is mild variation in the nuclei size of the myocardial fibers (short arrows). H&E × 40. B: Left ventricle in a 14 year old SWMC girl. Isolated small foci of mononuclear cells are observed (head arrows). H&E × 60. C: Right ventricle in a NMC 11 month old boy. Two mast cells are observed with different degrees of degranulation. The mast cell on the right (short arrow) exhibits significant decrease in the number of cytoplasmic granules. The mast cell on the left is well granulated. Toluidine blue × 100. D: Right ventricle in a 19 year old SWMC male. There are perivascular degranulated mast cells (head arrows). The granules can be observed in the interstitial space (short arrows). Myocardial fibers are labeled mI. Toluidine blue 1 μm section × 40. E: Right ventricle epicardial nerve in a 14 year old SWMC girl. There are mast cells located in the epineurial (arrowhead) and endoneurial (short arrows) spaces. Endoneurial mast cells (short arrows) are partially degranulated. Toluidine blue 7 μm section × 100. F: Electron micrograph of right ventricle arteriole in a SWMC 19 years old male. The luminal red blood cell (RBC) shows several nanosize particle-like material (average size 28 nm) (head arrows) and similar size particulate-like material is seen in the endothelial basement membrane (long arrow), and the smooth muscle cell nucleus and cytoplasm (white arrow). EM × 20,000.

Fig. 3.

RT-PCR left and right ventricular mRNA statistical results for IL1β, TNF α, IL10, CD14, NLCR1 and NLRP3 in SWMC and NMC subjects.