Table 2. Studies investigating the effects of PM_2.5 in cardiovascular homeostasis and function.

This table summarizes in vitro and in vivo studies published to date investigating the physiological effects of PM_2.5 in cardiovascular system, which show association between PM_2.5 intoxication and CVDs. PM; particulate matter. NIST; National Institutes of Standards and Technology. eNOS; endothelial nitric oxide synthase.

Disease type	Phenotype	Species	Species or cell lines used for investigation	Exp. Type	Treatment method	Treatment dosage & duration	Source of PM2.5	Ref.
Cardiac dysfunction	Cardiac ATP synthesis abnormality	Rat	H9c2 (rat cardiomyocyte cell line)	In vitro	Submerged cell culture	1–10 μg/cm2 PM2.5 for 24 h	Taiyuan, China	[29]
Cardiac dysfunction	Functional cardiotoxicities, mitochondrial dysfunction, DNA damage	Rat	Neonatal rat cardiomyocyte (NRCM)	In vitro	Submerged cell culture	25, 50, 75, 100, 200 and 400 μg/ml for 48 h	Taiyuan, China	[55]
Cardiac dysfunction	Contractile dysfunction, reduced calcium handling ability	Rat	Sprague Dawley (SD) rat cardiomyocytes	In vitro	Submerged cell culture	0.25, 0.50, 1.0, and 25 μg/ml for 1h	Diesel exhaust particle (DEP), NIST Standard Reference Matter (SRM) 1650b	[64]
Cardiac dysfunction	Exacerbates High Glucose-Induced Cardiomyocyte Dysfunction through ROS Generation	Rat	Sprague Dawley (SD) rat cardiomyocytes	In vitro	Submerged cell culture	0.1 μg/ml for 24h	Diesel exhaust particle (DEP), NIST Standard Reference Matter (SRM) 1650b	[54]
Cardiac dysfunction	Mitochondria-mediated apoptosis	Human	AC16	In vitro	Submerged cell culture	25, 50, and 100 μg/ml for 24h	Beijing, China	[58]
Cardiac dysfunction	Cardiac ATP synthesis abnormality; functional decrement of myocardium	Rat	Sprague Dawley (SD) rats	In vivo	Intratracheal instillation	summer PM2.5 groups (0.2, 0.6, 1.5 mg/kg, and winter PM2.5 group (0.3, 1.5, 2.7 mg/kg), once every 3 days for 2 months	Taiyuan, China	[29]
Cardiac dysfunction	Cardiac fibrosis	Mouse	C57BL/6 mice	In vivo	Oropharyngeal aspiration	3 mg/kg every other day for 4 weeks	Taiyuan, China	[36]
Cardiac dysfunction	Myocardial Ischemia/Reperfusion Injury Through Farnesoid-X-Receptor-Induced Autophagy	Rat	Sprague Dawley (SD) rats	In vivo	Intratracheal instillation	6.67 mg/ml for 24 h	Lanzhou, China	[60]
Cardiac dysfunction	Autophagy; decreased myocardial layers in the heart	Zebrafis h	Zebrafish embryos; wildtype zebrafish (AB strain) and transgenic zebrafish (Tg:zlyz-enhanced green fluorescent protein (EGFP))	In vivo	Submerged cell culture	200, 300, 400, 500, 600, and 800 μg/ml for 120 h	Jinan, China	[56]
Cardiac dysfunction	Fibrosis, myocardial remodeling, inflammatory response, oxidative stress	Rat	Wistar rats	In vivo	Exposure chamber	daily average of between 600–800 μg/m3, 5 days a week, for 4 weeks, or 7 weeks	São Paulo, Brazil	[52]
Cardiac dysfunction	Fibrosis, myocardial remodeling, inflammatory response, oxidative stress	Mouse	BALB/c mice	In vivo	Intratracheal instillation	4.0 mg/kg, once per day for 5 consecutive days	China	[49]
Cardiac dysfunction	Cardiomyopathy confers susceptibility to particulate matter-induced oxidative stress, vagal dominance, arrhythmia, and pulmonary inflammation	Rat	Spontaneously Hypertensive Heart Failure (SHHF) rats	In vivo	24-port nose-only flow-by inhalation chambers	580 μg/m3 for 4h	Synthesized by combining metal compounds in molar ratios comparable to those in the historic residual oil fly ash (ROFA) sample collected as a postcontrol fugitive stack emission at a Florida Power and Light plant burning #6 grade residual oil containing 1% sulfur	[67]
Cardiac dysfunction	Cardiac and mitochondrial dysfunction	Rat	Sprague Dawley (SD) rats	In vivo	Intratracheal instillation	300 μl of vehicle (5% FBS in PBS) with 300 μg of PM for 24 h	Collected within one mile of an active mountaintop removal mines (MTM) site	[59]
Cardiac dysfunction	Exacerbation of viral myocarditis	Mouse	BALB/c mice	In vivo	Intratracheal instillation	10 mg/kg for 7d	Non-industrial district in Shanghai, China	[41]
Cardiac dysfunction	Exacerbation of viral myocarditis	Mouse	BALB/c mice	In vivo	Intratracheal instillation	10 mg/kg for 7d	Non-industrial district in Shanghai, China	[42]
Cardiac dysfunction	Systemic oxidative stress	Mouse	ApoE−/− mice, C57BL/6 mice	In vivo	Intratracheal instillation	3, 10, or 30 mg/kg for 3d	Shanghai, China	[69]
Cardiac dysfunction	Inflammation, oxidative stress, hypercoagulation, cardiomyocyte apoptosis	Rat	Wistar rats	In vivo	Intratracheal instillation	0, 4, 40 mg/kg once every 2d for 3 times	Beijing, China	[53]
Cardiac dysfunction	Inflammation, imbalance of oxidative stress, the altered Ca2+ channel related proteins and the increased intracellular free Ca2+, heart impairment	Mouse	BALB/c mice	In vivo	Intratracheal instillation	0.01 mg/μl for 2d	Hebei, China	[46]
Cardiac dysfunction	Cardiomyopathy, oxidative stress, fibrosis, inflammation, mitochondrial disorder	Mouse	C57BL/6J mice; wild type (Nrf2+/+) and Nrf2 knockout (Nrf2−/−) mice	In vivo	Exposure chamber	50.1 ± 2.5 μg/m3, flow rate of 65 L/min for 6 h/day, 5 times a week, for 24 weeks	Yuquan Road, Beijing, China	[47]
Cardiac dysfunction	Cardiac hypertrophy, fibrosis, metabolic alterations	Mouse	C57BL/6J mice	In vivo	Exposure chamber	100 μg/m3, flow rate 3.5-4.0 L/min, exposed for 28 consecutive days (6 h/day), with 2 days of break every 5 days	Taipei Main Station, Taiwan	[10]
Cardiac dysfunction	Increased glycemic homeostasis, inflammation, myocarditis, aortic medial thickness	Rat	Sprague Dawley (SD) rats	In vivo	Exposure chamber	PM2.5 at ambient concentration for 24 h/day, 7 days/week, for a total of 16 weeks	Taipei City, Taiwan	[43]
Cardiac dysfunction	Impaired oxygen metabolism and contractile function	Mouse	Swiss mice	In vivo	Intranasal instillation	1 mg/kg	Mystic, Connecticut, USA	[91]
Cardiac dysfunction	Systemic adverse effects, alterations in lung and cardiac gene expression	Mouse	BALB/c mice	In vivo	Intratracheal instillation	100 μg of PM2.5 in 100 μl of isotonic saline solution on d0, d3, d6	Milan, Italy	[50]
Cardiac dysfunction	Systemic and pulmonary inflammation, decreased left ventricular ejection fraction, pulmonary and myocardial fibrosis and oxidative stress	Mouse, human	C57BL/6J mice and AMPKα2−/− mice for in vivo, human bronchial epithelial BEAS-2B cells and rat cardio myoblast H9C2 cells for in vitro	In vivo, in vitro	Intratracheal instillation, Submerged cell culture	10 mg/kg PM2.5 in 10 μl PBS every other day for 4w in vivo, 24h in vitro	China	[88]
Vascular dysfunction	Vascular inflammation, decreased viability, migration and angiogenesis	Human	Human umbilical vein endothelial cells (HUVECs), human microvascular endothelial cells (HMEC-1)	In vitro	Submerged cell culture	0–800 μg/ml for 6h	NIST Standard Reference Matter (SRM)	[77]
Vascular dysfunction	Autophagy, FHL2 upregulation, IL-6 production, activation of NF-κB pathway	Mouse	Mouse aortic endothelial cells (MAECs)	In vitro	Submerged cell culture	100 μg/ml for 24 h	Beijing, China	[63]
Vascular dysfunction	Oxidative stress and reduced the PAI-1 production of endothelial cells	Rat	Rat heart microvessel endothelial (RHMVE) cells	In vitro	Submerged cell culture	0, 5, 10, and 25 μg/ml for 12h	Saitama, Japan	[78]
Vascular dysfunction	Vascular remodeling, exacerbated transition from left ventricular failure to right ventricular hypertrophy	Mouse	BALB/c mice	In vivo	Exposure chamber	Local PM2.5 for 10h each day for 3w	Beijing, China	[66]
Vascular dysfunction	Atherosclerosis progression, activation of circulating leukocytes, platelets and associated inflammatory factors	Mouse	ApoE−/− mice	In vivo	Intratracheal instillation	30 mg/kg each day for 8w	Shijiazhuang, China	[80]
Vascular dysfunction	Disseminated intravascular coagulation, inflammatory response, vascular endothelial injury and prothrombotic state	Rat	Sprague Dawley (SD) rats	In vivo	Intratracheal instillation	0, 1.8, 5.4 and 16.2 mg/kg every 3 days for 30d	Beijing, China	[84]
Vascular dysfunction	Autophagy, VEGF induction, inflammation	Rat	Sprague Dawley (SD) rats	In vivo	Intratracheal instillation	1.5 mg/kg every 2d for 3 times	Wuhan, China	[86]
Vascular dysfunction	Intracraneal atherosclerosis	Rat	Sprague Dawley (SD) rats	In vivo	Exposure chamber	Ambient PM2.5 for 6w or 12w	Beijing, China	[89]
Vascular dysfunction	Endoplasmic reticulum instability, ANGII-dependent endothelial dysfunction	Rat	Sprague Dawley (SD) rats	In vivo	Intratracheal instillation	1.5 mg/kg every 2d for 3 times	Wuhan, China	[83]
Vascular dysfunction	Endothelial dysfunction, decreased endothelium-dependent relaxation and eNOS expression on pulmonary arteries associated with local inflammation	Rat	Wistar rats	In vivo	Exposure chamber	Ambient PM2.5 (approx. 600 μg/m3) for 2w	São Paulo, Brazil	[82]
Cardiac dysfunction	Heart failure, acute inflammatory response, chronic matrix remodeling, electrical remodeling, epigenetic changes	Mouse	FVB mice	In utero	Exposure chamber	average concentration of 73.61 μg/m3, for 6h/day, 7 days/week	Columbus, Ohio, USA	[51]
Cardiac dysfunction	Neonatal cardiac dysfunction	Mouse	FVB mice	In utero	Exposure chamber	average concentration of 91.87 μg/m3, for 6h/day, 5 days/week throughout gestation period (20 days)	Columbus, Ohio, USA	[65]
Cardiac dysfunction	Cardiac dysfunction	Mouse	FVB mice	In utero	Exposure chamber	average concentration of 38.58 μg/m3 for 6 hours/day, 5 days/week for 3 months	Columbus, Ohio, USA	[48]