Functional, Cellular, and Molecular Remodeling of the Heart under Influence of Oxidative Cigarette Tobacco Smoke

Table 2

A selective list of studies highlighting the effect of drugs on LV remodeling after CS exposure.

Model	Study/drug tested/effect^¥	Cardiac remodeling						Ref
		Structural/functional	Inflammation	Oxidative stress	Apoptosis	Metabolic impairment	Others
S-D rats: 40 cigs/day for 4 months	H2S effects on LV remodeling in rats subjected to CS Protection: ++	↓ LVEDD and LVESD; ↑ LVEF and LVFS	N/A	↓ ROS; ↓ MDA levels; ↑ SOD and GSH-Px activities	N/A	N/A	↓ fibrosis	[125]
S-D rats: 4 cigs/day/5 days/week for 6 weeks with MI on the 5^th week	N-acetyl cysteine effects on LV remodeling post-MI in rats subjected to CS Protection: ++	↓ infarct size; ↑ LVFS; ↓ LVESD ↔ LVEDD	↓ serum levels of IL-1α, IL-1β, IL-2, IL-6, IFN-γ and TNF-α; ↓ cardiac mRNA expression of IL-6, IFN-γ, SDF-1, TGF-β, and TNF-α	↑ cardiac mRNA of SOD, TXN; ↓ cardiac mRNA of p22^phox, Keap, and Nrf2; ↑ plasma levels of glutathione	↓ PARP	N/A	↓ mRNA of MMP-2	[78]
Wistar rats: 40 cigs/day/5 days/week for 2 months	Effects of swimming on LV remodeling in rats subjected to CS Protection: −	↑ LVM, LVEDP, LVH, RVH	N/A	N/A	N/A	N/A	↓ RV and LV collagen	[126]
		(i) Impairment of myocardial inotropism
Wistar rats: 40 cigs/day for 6 months starting at 48 hours post-MI	Effects of β-carotene on LV remodeling post-MI in rats subjected to CS; Protection: −	↔ infarct size; ↑ MCA	N/A	N/A	N/A	N/A	N/A	[127]
Wistar rats: 40 mg/kg/day of tobacco smoke for 2 months	Propranolol effects on LV remodeling in rats subjected to CS Protection: +	↓ LVM : BW ratio, HR	N/A	N/A	N/A	N/A	N/A	[128]
Wistar rats: 40 cigs/day for 2 months	Lisinopril effects on LV remodeling in rats subjected to CS Protection: +	↓ LVESD, CSA, LVW; ↑ LVEF, LVFS	↔ IFN-γ, TNF-α cardiac protein levels	N/A	N/A	N/A	↔ connexin 43 protein levels; ↔ collagen amount	[28]
Wistar rats: 40 cigs/day for 2 months	Taurine effects on LV remodeling in rats subjected to CS Protection: −	↑ LVWT, E/A,; ↑ diastolic dysfunction	↔ IFN-γ, TNF-α cardiac protein levels	N/A	N/A	↑ LDH activity	↓ Ser16P-PLN; ↓ P-PLN : PLN ratio; ↔ collagen; volume	[129]
Albino guinea pigs: 5 cigs/day for 2 months	Vitamin C effects on LV remodeling in guinea pigs subjected to CS; Protection: ++	N/A	(i) Prevents neutrophil infiltration	↓ oxidative damage	↓ apoptosis	N/A	(i) No troponin T and I serum levels	[9]
							(ii) No thrombosis
			↓ TNF-α, IL-1β cardiac protein levels				↓ fibrosis, collagen deposition; ↓ LDL, TG serum levels; ↓ MMP-9, 12
Rats: 2 months of CS exposure	Vitamin D effects on LV remodeling in rats subjected to CS Protection: +	↓ LVH	↔ IFN-γ, TNF-α and IL-10	↓ LOOH; ↑ SOD, catalase activities	N/A	N/A	↔ collagen deposition	[123]
Wistar rats: 40 cigs/day for 4 months	Trimetazidine effects on LV remodeling in rats subjected to CS; Protection: ++	↓ LVW : BW ratio; ↑ LVEF, LVFS,; ↓ LVEDD, LVESD	↓ IL-1β, IL-6, and TNF-α cardiac mRNAs; ↓ IL-1β, IL-6, and TNF-α serum levels	↓ MDA levels; ↑ SOD and GSH-Px activities	↓ apoptosis	N/A	↓ fibrosis	[60]
S-D rats: 96 cigs/day passive for 6 weeks	L-arginine effects on LV remodeling post-I/R in rats subjected to passive CS; Protection: +	↓ infarct size; ↔ HR, SP	N/A	N/A	N/A	N/A	↔vascular reactivity; ↔ bleeding time	[130]
Wistar rats: 40 cigs/day for 4 months	H2S effects on LV remodeling in rats subjected to CS; Protection: ++	↑ LVEF, LVFS; ↓ LVEDD, LVESD	N/A	N/A	↓ apoptosis	N/A	↓ autophagy	[30]
Wistar rats: 40 cigs/day for 3 months	3-Methyladenine effects on LV remodeling in rats subjected to CS; Protection: ++	↓ LVEDD, LVESD; ↑ LVFS, LVEF	N/A	N/A	N/A	N/A	↓ autophagy; ↓ Beclin1, LC3	[93]
Wistar rats: 40 cigs/day for 4 months	Valsartan effects on LV remodeling in rats subjected to CS; Protection: ++	↓ LVEDD, LVESD; ↑ LVFS, LVEF	↓ hs-CRP, IL-6, TNF-α and MCP-1 serum levels	↓ MDA; ↑ SOD and GSH-Px activities	↓ apoptosis	N/A	N/A	[76]
Rabbits: 6 cigs/day passive or 3 weeks	Captopril effects on LV mitochondria in rabbits subjected to passive CS; Protection: +	N/A	N/A	N/A	N/A	(i) Prevents Mito coQ10 decrease	N/A	[26]
						(ii) Improves OXPHOS
						↑ F1-ATPase levels; ↑ cytooxidase activity
Rats: 20 cigs/day first week then 40 cig/day for two months	Pentoxifylline effects on LV remodeling in rats subjected to CS; Protection: +	↓ LA area; ↑ LV systolic function	↔ IL-10, ICAM-1, TNF-α	↑ SOD and GSHPx activities	↔ caspase-3	↓ LDH, CS, 3-OH-DHA	N/A	[90]
Wistar rats: 40 cigs/day for two months	Spironolactone effects on LV remodeling in rats subjected to CS; Protection: 0	↔ cardiac hemodynamics and structure	↔ IFN-γ, TNF-α, IL-10, ICAM-1	N/A	N/A	N/A	↔ GLUT4; ↔ collagen volume	[79]

^¥Results presented in this table are in comparison with nonsmoking same conditioning treatment. CS: chronic tobacco smoking; N/A: not available; ↑, increase; ↓, decrease; ↔, no changes; H2S: hydrogen sulfide; LV: left ventricle; LVEDD: left ventricular end-diastolic diameter; LVESD: left ventricular end-systolic diameter; LVEF: left venticular ejection fraction; LVFS: left ventricular fractional shortening; LVEDP: left ventricular diastolic pressure; LVWT: left ventricular wall thickness; LVH: left ventricular hypertrophy; RVH: right ventricular hypertrophy; LDL: low-density lipoprotein; TG: triacylglycerols; SOD: superoxide dismutase; GSH-Px: glutathione peroxidase; MDA: malondialdehyde; MI: myocardial infarction; IL: interleukin; IFN: interferon; TNF: tumor necrosis factor; SDF-1: stromal cell-derived factor 1; TGF: transforming growth factor; TXN: thioredoxin; mRNA: messenger RNA; p22^phox, cytochrome b₅₅₈ α-subunit; Keap: Kelch-like ECH-associated protein 1; Nrf2: nuclear factor (erythroid-derived 2)-like 2; PARP: poly [ADP-ribose] polymerase 1; MMP: matrix metalloproteinases; RV: right ventricle; LVM : BW: left ventricular mass : body weight; HR: heart rate; LVW: left ventricular weight; CSA: cross-sectional area; LDH: lactate dehydrogenase; Ser16 P-PLN: serine 16 phosphorylated phospholamban; P-PLN : PLN: phosphorylated phosfolamban/phospholamban ratio; E/A: E: peak velocity of early ventricular filling, A, peak velocity of transmitral flow during atrial contraction; Mito coQ10: mitochondrial coenzyme Q₁₀; LC3: microtubule-associated protein 1A/1B-light chain 3; hs-CRP: C-reactive protein; MCP-1: monocyte chemotactic protein-1; OXPHOS: oxidative phosphorylation chain; LA: left atria; ICAM-1: intercellular adhesion molecule 1; 3-OH-DHA: 3-hydroxyacyl coenzyme A dehydrogenases; GLUT4: glucose transporter type 4.