Antifibrotic Effects of Antioxidant N-Acetylcysteine in a Mouse Model of Human Hypertrophic Cardiomyopathy Mutation
Ali J. Marian, MD, FACC*,
Vinitha Senthil, PhD,
Suet N. Chen, MS and
Raffaella Lombardi, MD
Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, Texas
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Figure 1 Plasma and myocardial levels of lipid peroxides. Myocardial (A) and plasma (B) levels of malondialdehyde (MDA) and 4-hydroxyalkenals (HAE) are depicted in non-transgenic (NTG) and cardiac troponin T-Q92 (cTnT-Q92) transgenic mice treated with placebo or with N-acetylcysteine (NAC). *p < 0.05 for pairwise comparisons.
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Figure 2 Effect of NAC on CVF. Panels in 2A show representative high-magnification microscopic fields (x400) in non-transgenic (NTG), cTnT-Q92 mice treated with placebo and cTnT-Q92 mice treated with NAC. (B) Quantitative values in the three groups. *p < 0.05 for pairwise comparisons.
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Figure 3 Expression levels of procollagen genes. Relative expression levels, corrected for the levels in NTG mice, are depicted for Col1a1, Col1a2, and Col3a1 procollagen genes.
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Figure 4 Oxidized nuclear and mitochondrial DNA levels. (A) mtDNA isolated and digested with BamH1 restriction enzyme, which results in two bands of approximately 8 and 9 kbp, indicating the purity of the isolated mtDNA. (B) Immuno-slot blot of mtDNA (upper blot) and the corresponding ethidium bromide stained blot (lower blot) in three mice in each of the experimental groups. (C) Immuno-slot blot (upper blot) of nuclear DNA and ethidium bromide stained blot (lower blot) in three mice per experimental group.
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Figure 5 Expression levels of selected signaling kinases. (A) Immunoblots showing expression levels of phosphorylated and total p44/42, p38, and JNK. (B, C, and D) Quantitative analysis of the relative levels of phosphorylated p44/42, p38, and JNK, respectively, all normalized to levels in the corresponding NTG group, in the experimental groups. The sum of density of 44 and 42 kDa bands were used to quantify levels of p44/42. Similarly, the sum density of 46 and 54 kDa bands were used for quantification of JNK. *p < 0.05 for pairwise comparisons.
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