Table 3.

Summary of effects of vehicular emissions and black carbon on CVD health endpoints

Health endpoint	In vitro studies	In vivo studies	Human panel studies
1. Oxidative stress	Li et al. 2002a (increases in HO-1, diesel PM)	McDonald et al. 2004 (diesel emissions, increased HO-1 in normal mice; oxidative stress abolished with use of catalyzing trap which totally eliminated black carbon, largely eliminated most organics, including many PAHs)	Mills et al. 2005 (diesel emissions, healthy human volunteers; reduction in t-PA, impairment of vascular tone, postulated by authors to be related to oxidative stress; also see HRV Alteration [HRV changes often caused by oxidative stress])
	Li et al. 2002b (increases in HO-1, Los Angeles air)		Delfino et al. 2008 (decreased levels of anti-oxidant enzyme activity, in panel of 29 non-smoking elderly subjects with history of coronary artery disease associated with BC, NO2, primary OC of outdoor origin, and ultrafine PM, for current day and multi-day averages, in study with excellent exposure characterization, using both indoor and outdoor monitors at Los Angeles residences)
	Li et al. 2003 (increases in HO-1, most harm caused by ultrafines in Los Angeles air, correlated with organics and PAHs)
2. HRV alteration	NA	Anselme et al. 2007 (diesel emissions, HRV decreases in healthy and CHF rats immediately after exposure)	Adar et al. 2007 (changes in six different types of HRV associated with BC exposure; when subjects on bus with high BC levels, larger HRV changes roughly correspond with larger changes in BC; monitor followed subjects wherever they went)
			Schwartz et al. 2005b (changes in 4 types of HRV associated with BC concentrations, but not with concentrations of non-BC regional PM2.5; subjects live on same road as monitor is located, both in close proximity to road, 0.5 miles apart)
			Creason et al. 2001 (HRV changes monotonically associated with increasing PM2.5, after two days with high PM2.5 from only rural sources eliminated from regression)
			Ebelt et al. 2005 (HRV associations found for ambient urban PM, not found for sulfate; personal monitors used)
			In studies using central monitors, Wheeler et al. (2006) and Park et al. (2005) show associations with BC in only one fourth of tests; Luttmann-Gibson et al. (2006) find no BC associations.
			Park et al. (2007) is same study as Park et al. (2005), but uses wind trajectories to determine sources, thus has better exposure information than Park et al. (2005); HRV associations found for urban air masses, not for rural air masses
3. ST-segment Depression	NA	Yan et al. 2008 (diesel exhaust particles impaired left ventricular functioning in healthy rats, with further impairment in rats with myocardial injury)	Mills et al. 2007 (ST-segment depression in subjects with CHD exposed to diesel emissions twice as great as for subjects without CHD, suggesting how diesel emissions could harm susceptible subjects)
			Gold et al. 2005 (in parallel study to Schwartz et al. 2005b HRV study, e.g., with accurate exposure information, ST-segment depression associated with BC but not with PM2.5)
			Lanki et al. 2006 (in study of several local and regional pollutants lacking good exposure information, ST-segment depression associated with ABS [EU equivalent of BC] but not with sulfate or other pollutants)
4. Cardiac Arrhythmia	NA	Anselme et al. 2007 (diesel emissions, 200% to 500% increase in ventricular premature beats in CHF rats, but not in normal rats)	Albert et al. 2007 (risks of ICD shock elevated in hour after driving, RR = 2.24; risks for ventricular fibrillation or tachycardia elevated in half hour after driving, RR = 4.46)
			Riediker et al. 2004a, b (∼40% increase in SVE beats for change of one SD in “speed change” factor reflecting diesel emissions and brake wear)
			Ebelt et al. (2005) (SVE associations found for ambient urban PM, non-sulfate ambient urban PM, not found for sulfate; personal monitors used)
			Peters et al. (2000), Dockery et al. (2005), Metzger et al. (2007), and Sarnat et al. (2006) are extant studies of arrhythmias using central monitor concentrations as proxies for subject exposure over large metropolitan areas, causing exposure misclassification; first study finds larger associations with vehicular emissions (BC and NO2) than with PM2.5; second study finds traffic emissions more likely cause of arrhythmias; third study finds no associations; associations in fourth study are with sulfate but not with BC; the first three studies discuss exposure misclassification as possible reason for underestimates of associations
5. Vascular Function	Miller et al. 2009 (diesel particles reduce bioavailability of endothelium-derived NO in aortic rat rings in vitro via oxidative stress, without prior interaction with lung or vascular tissue)	Bartoli et al. 2009 (increases in mean, systolic and diastolic blood pressure found in dogs exposed to CAPs taken from near major urban roadway; BC, carbonaceous particle count associated with increases in blood pressure)	Urch et al. 2004 (significant increase in vasoconstriction in healthy human volunteers exposed to CAPs taken from near freeway associated only with EC and OC among 25 components of PM2.5 analyzed)
	Campen et al. 2005 (fresh diesel emissions and filtered diesel exhaust cause vasoconstriction in mice ex vivo, aldehydes and alkanes most likely involved)		Urch et al. 2005 (significant increase in blood pressure in healthy human volunteers exposed to CAPs taken from near freeway, possibly associated with increase in vasoconstriction in 2004 study, related to traffic emissions)
			Auchincloss et al. 2008 (in subjects aged 45–84, systolic blood pressure and pulse pressure associated with increased PM2.5 only when traffic variables (NO2 levels above median value; residence within 300 m of highway; or high density of roads near residence) were “positive,” not when traffic variables were “negative”)
			Lai et al. 2005 (toll workers exposed to traffic exhaust had significantly higher levels of plasma NO, which affects vascular tone)
			Peretz et al. 2007 (in healthy adult volunteers, diesel exhaust preferentially modulated genes involved in oxidative stress, inflammation, leukocyte activation and vascular homeostasis)
			Peretz et al. 2008 (in adult volunteers exposed to diesel exhaust, reduction in brachial artery diameter linearly related to increasing concentration of exhaust; plasma levels of endothelin-1, a vasoconstrictor, significantly increased only at 200 μg/m3 of diesel exhaust, but not at 100 μg/m3)
6. Inflammation	Bonvallot et al. 2001 (diesel emissions and diesel organic extracts induced increased levels of pro-inflammatory NF-κB in human bronchial epithelial cells; less intensive effects induced by stripped carbonaceous core)	McDonald et al. 2004 (increased levels of three inflammatory biomarkers (TNF-α, IL-6, and INF-γ) associated with exposure to diesel emissions, effects abolished with use of new catalyzing trap which eliminated BC completely, largely eliminated most organics, including many PAHs)	Delfino et al. 2008 (several biomarkers for inflammation [CRP, IL-6, TNF-α receptor] significantly increased with increased concentrations of BC, EC, CO, primary OC, and with increased particle number)
			Riediker et al. 2004a (CRP elevated with increased in-vehicle PM, in study of patrol officers after 9-h shift)
			Riediker 2007 (IL-6 elevated with increased in-vehicle PM, in study of patrol officers after 9-h shift)
			Tornquist et al. 2007 (diesel emissions increased TNF-α, IL-6 levels in healthy human volunteers, vs. filtered air)
			Zeka et al. 2006 (elevated BC levels, recorded at central monitor, associated with increased CRP levels in the obese, and in those lacking a measure of genetic protection against oxidative stress, e.g., GSTM1-null subjects. Authors discuss exposure misclassification, note that they would expect larger risks with better exposure assessment)
7. Atherosclerosis and lipoperoxidation	See oxidative stress and inflammation sections for in vitro work relevant to atherosclerosis, caused in large part by systemic interaction of oxidative stress and inflammation	Araujo et al. 2008 (increased early atherosclerotic lesions in ApoE -/- mice breathing CAPs ambient in PAHs from near LA freeway, exposure to ultrafine PM inhibited anti- inflammatory capacity of plasma HDL)	Sharman et al. 2002 (auto mechanics, regularly exposed to higher levels of vehicular emissions than controls, had significantly higher susceptibility of plasma to oxidation)
	Gong et al. 2007 (interaction between oxidized LDL lipids and organic diesel emission extracts affects gene expression relevant to vascular inflammation and atherosclerotic pathways in human microvascular endothelial cells; work then replicated in vivo, with similar findings – see in vivo, next column)	Gong et al. 2007 (interaction between oxidized LDL lipids and concentrated ultrafine diesel exhaust particles in Los Angeles air affects gene expression corresponding to atherosclerotic pathways in mice, viewed by authors as confirming in vitro findings in column to left)	Delfino et al. 2008 (levels of soluble P-selectin, important for platelet activation in atherosclerosis, significantly associated with increased levels of EC of outdoor origin, primary OC, in study of seniors in Los Angeles)
	Huang et al. 2003 (PM1.0 more likely to cause lipoperoxidation in human lung cells than larger fractions, OC and EC but not various ions associated with this effect)