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

Table 1

A selective list of studies highlighting the effect of CS on cardiac remodeling.

Model	Study design^¥	Cardiac remodeling						Ref
		Structural/functional	Inflammation	Oxidative stress	Apoptosis	Metabolic impairment	Others
C57BL/6J mice: 32 weeks of CS exposure	CS effect on LV remodeling in mice	↑ SBP, DBP; ↑ HW : BW ratio, LVM; ↓ EDV and CO	N/A	↑ ROS in white blood cells	N/A	N/A	↑ NO decay; ↑ ED	[22]
		(i) Impaired LV P-V relationship at high afterload
S-D rats: 1 week CS exposure prior to abdominal aortocaval fistula surgery and for 6 weeks thereafter	CS effect on LV remodeling in volume overloaded heart	↑ LV dilation; ↓ LVPWT, eccentric index, FS; ↔ HR, CO, BP	N/A	N/A	N/A	N/A	↓ collagen; deposition; ↓ ET-1, HIF1α, VEGF, TGF-β protein levels; ↑ MMP-9, TIMP-1 protein levels; ↔ MMP-2 protein levels	[29]
S-D rats: 5 weeks of CS exposure	CS effect on LV remodeling in rats	↑ LVEDD, LVESD, E/A; ↑ HW : BW ratio; ↓ FS; ↔ LVPWT	N/A	N/A	N/A	N/A	↑ urinary NE levels; ↑ Pp38/total p38; ↑ PERK1/2/ERK1/2; ↔JNK levels	[23]
Rabbit-mouse VM exposed to 0.1% aqueous extract of cig smoke	Effects of aqueous extract of cigs on isolated VM	↑ ischemic injury; ↑ myocyte contracture	N/A	↑ ROS	N/A	↑ susceptibility to mPTP opening	↑ myocyte mito [Ca2+]m uptake; ↑ myocyte cytosolic [Ca2+]i during ischemia	[89]
Wistar rats: 20 cigs/day first week then 40 cigs/day for 4 weeks	CS effect on cardiac Cx43	↔ LVW, RVW, CSA	N/A	N/A	N/A	N/A	↔ Cx43 distribution at intercalated disks; ↓ Cx43 intensity at intercalated disks; ↑ Cx43 dephosphorylation; ↑ lateralization; ↔ total Cx43 levels; ↔ CVF	[27]
Wistar rats: 20 cigs/day first week then 40 cigs/day until 2 months	CS effect on LV remodeling	↑ LA area, CSA; ↑ LVSV; ↓ EF, FS	N/A	↑ ROS; ↓ SOD and GSHPx activities	↑ apoptosis	↓ OHDAH, CS activities; ↑ LDH activity; ↑ serum VLDL, LDL, TG, myocardial TG; ↓ serum HDL	↔ PPAR-α, PGC-1α	[24]
Wistar rats: 6 months of CS exposure starting at 48 hours post-MI	CS effect on LV remodeling post-MI	↑ HR, LA area, E/A, DA, SA; ↑ RVW : BW ratio, LW	N/A	↑ GSH, GSSG; ↓ GSH/GSSG ratio; ↔ LOOHs levels	N/A	N/A	↔ CVF	[25]
C57BL/6 mice: 20 cigs/day for 1 month	CS effect on LV remodeling	↑ BP, LVH, HW : BW ratio; ↔ HR	↑ IL-6, TNF-α serum levels; ↔ IL-6, TNF-α	N/A	N/A	N/A	↑ eNOS, iNOS, sGCα, sGCβ, pVASP, cGMP; ↑ mRNA β-MHC; ↔ PKG, PDE5; ↓ H2S producing enzymes	[124]
C57BL/6 mice: 20 cigs/day for 1 month	CS effect on LV remodeling followed by NoC, PreC or PostC I/R	↔ infarct size (NoC, PreC); ↑ infarct size (PostC)	N/A	↔ PC, MDA (NoC, PreC); ↑ PC, MDA (PostC)	N/A	N/A	↔ Akt, eNOS, cGMP activation (PreC); ↓ Akt, eNOS, cGMP activation (PostC); ↔ Akt, ↑ eNOS, and cGMP (NoC); ↓ pVASP (PostC and PreC); ↑ pVASP (NoC); ↓ nitrate + nitrite (PostC and PreC); ↔ nitrate + nitrite (NoC)	[124]

^¥Results presented in this table are in comparison with nonsmoking same conditioning treatment. CS: chronic tobacco smoking; S-D: Sprague-Dawley; N/A: not available; ↑, increase; ↓, decrease; ↔, no changes; SBP: systolic blood pressure; DBP: diastolic blood pressure; LV: left ventricle; LVM: left ventricular mass; EDV: end-diastolic volume; CO-Hb: carboxyhemoglobin; LV P-V: LV pressure-volume; ED: endothelial dysfunction; HW : BW: heart weight : body weight; ROS: reactive oxygen species; NO: nitric oxide; LVPWT: left ventricular wall thickening; FS: fractional shortening; HR: heart rate; BP: blood pressure; ET-1: endothelin 1; HIF1α, hypoxia inducible factor; VEGF: vascular endothelial growth factor; TGF-β: transforming growth factor; MMP: matrix metalloproteinases; TIMP-1: tissue inhibitors of metalloproteinase-1; LVEDD: left ventricular end-diastolic diameter; LVESD: left ventricular end-systolic diameter; E/A: E: peak velocity of early ventricular filling, A: peak velocity of transmitral flow during atrial contraction; NE: norepinephrine; p38: p38 kinase; Pp38: phosphorylated p38 kinase; ERK: extracellular-regulated kinase; PERK: phosphorylated extracellular-regulated kinase; JNK: c-Jun NH2-terminal protein kinase; MPT: mitochondrial permeability transition; [Ca2+]i: intracellular calcium; [Ca2+]m: mitochondrial calcium; VM: ventricular myocytes; CVF: collagen volume fraction; RVW: right ventricular weight; CSA: cross sectional area; Cx43: connexin 43; LA: left atria; LVSV: left ventricular systolic volume; EF: ejection fraction; OHDAH: 3-hydroxyacyl coenzyme-A dehydrogenase; LDH: lactate dehydrogenase; LDL: low-density lipoprotein; VLDL: very low-density lipoprotein; TG: triacylglycerols; HDL: high-density lipoprotein; PGC-1α: peroxisome proliferator-activated receptor gamma coactivator 1 alpha; PPAR-α: peroxisome proliferator-activated receptor alpha; DA: diastolic area; SA: systolic area; LOOHs: lipid hydroperoxides; LVH: left ventricular hypertrophy; RVW : BW: right ventricular weight : body weight; LW: lung weight; eNOS: endothelial nitric oxide synthases; iNOS: inducible NOS; IL: interleukin; TNF: tumor necrosis factor; sGC: soluble guanylate cyclase; VASP: vasodilator-stimulated phosphoprotein; pVASP: phosphorylated VASP; cGMP: cyclic guanosine monophosphate; mRNA: messenger RNA; β-MHC: myosin heavy chain beta; PKG: protein kinase G; PDE5: phosphodiesterase type 5 inhibitor; H2S: hydrogen sulfide; PC: protein carbonyl; NoC: no conditioning, PreC: preconditioning; PostC: postconditioning; I/R: ischemia reperfusion; MDA: malondialdehyde; Akt: RAC-alpha-serine/threonine-protein-kinase.