Abstract
Oxidized LDL (Ox‐LDL) and oxidative stress have been implicated in both atherosclerosis and congestive heart failure (HF) development. Here, we tested whether Ox‐LDL levels in left ventricular blood (LVB) might differ from those of venous peripheral blood (PB), and whether the level might depend on cardiac function. We also tested whether the LDL molecule is likely to have a longer residence time in the left ventricle of HF subjects with low ejection fraction (EF). The aim of this study was to determine Ox‐LDL levels, paraoxonase 1 (PON1) activity, and cholesterol efflux capacity (CEC) of PB and LVB, and correlate these values with LVEF. Sixty‐one HF patients underwent preoperative transthoracic echocardiographic assessment of ventricular function. LVEFs were determined using Simpson's biplane technique. LVB and PB levels of Ox‐LDL were determined, and PON1 activity and plasma cholesterol efflux capacity were measured. A significant increase in the levels of Ox‐LDL in LVB was noted as compared to levels in PB, even when EF was near normal. However, as ejection fraction decreased, the level of Ox‐LDL in PB approached that of the LVB. PON1 activity and cholesterol efflux studies indicated increased oxidative stress in LVB and a decreased ability to promote cholesterol efflux from lipid‐enriched macrophages. The results suggest that LVB is more oxidatively stressed compared to PB, and therefore LV tissue might be affected differently than peripheral tissues. We recently reported that brain natriuretic peptide (BNP), a marker for HF, is induced by Ox‐LDL, so it is possible localized factors within the LV could profoundly affect markers of HF.
Highlights
Oxidative stress plays a significant role in the pathogenesis of several cardiovascular diseases, including heart failure (HF) (Griendling and Fitzgerald 2003; Madamanchi et al 2005; Mueller et al 2005)
We report that the levels of Oxidized low-density lipoprotein (Ox-LDL) in the peripheral blood increased with decreasing ejection fraction (EF), approaching levels of Ox-LDL noted in the left ventricular blood (LVB)
Increased Ox-LDL levels were found in the left ventricular (LV) blood of subjects with lower EF, the levels differed less between LVB and peripheral blood (PB) in this circumstance
Summary
Oxidative stress plays a significant role in the pathogenesis of several cardiovascular diseases, including heart failure (HF) (Griendling and Fitzgerald 2003; Madamanchi et al 2005; Mueller et al 2005). It has been noticed that several plasma biochemical markers of oxidative stress were increased in HF subjects (Belch et al 1991; McMurray et al 1993; Keith et al 1998), suggesting the importance of oxidative stress mechanisms in congestive HF progression. Oxidized low-density lipoprotein (Ox-LDL) were suggested to play a key role in the development of atherosclerosis (Steinberg 1997). Plasma levels of Ox-LDL are considered to be a prognostic indicator of mortality in subjects with congestive HF (Tsutsui et al 2002). Increased levels of OxLDL and Ox-LDL antibodies in the plasma are correlated with a lower EF, increased severity of clinical symptoms (Tsutsui et al 2002; George et al 2006), and increased postinfarction left ventricular (LV) volumes (Fuji et al 2002)
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