Serum Phospholipid Transfer Protein Mass as a Possible Protective Factor for Coronary Heart Diseases

Abstract

n inverse relationship between high-density lipoprotein (HDL) cholesterol and cardiovascular diseases has been demonstrated in epidemiologic studies, 1,2 and is often explained by the capacity of HDL to transport cholesterol from peripheral tissues to the liver, known as reverse cholesterol transport. 3 In this process, pre--HDL, a quantitatively minor subfraction of HDL, is thought to play a critical role because it acts as an efficient acceptor in the cholesterol efflux process from the plasma membrane of peripheral cells. 3,4 Phospholipid transfer protein (PLTP) is capable of generating pre--HDL by inducing HDL conversion, a process that remodels a homogeneous HDL fraction into populations of large and small HDL particles. [5][6][7][8] The transfer of phospholipids to immature HDL in the process of HDL maturation is also essential in maintaining reverse cholesterol transport. 5,9,10 In addition, PLTP has other roles, such as the transfer oftocopherol to cell membrane for the maintenance of endothelial function, or the transfer of lipopolysaccharide to Circulation Journal Vol.68, January 2004 lipoproteins, which leads to neutralization of its potent inflammatory function. 5 Altogether, PLTP can be considered to play an important role in the prevention of atherosclerosis, and thus it has recently attracted much attention.Previous studies regarding PLTP examined its phospholipid transfer activity in patho-physiologic states in human or experimental models. 11-14 Sandwich enzyme-linked immunosorbent assay with 2 monoclonal antibodies to human PLTP has been recently introduced to assay PLTP concentration, 15,16 but the significance of the PLTP concentration in human diseases is incompletely understood. 5,17 It is, therefore, important to evaluate whether an elevated concentration of serum PLTP is associated with an increased or decreased risk of cardiovascular diseases. We examined serum PLTP in relation to newly diagnosed cardiovascular diseases in a middle-aged worksite-based cohort of men in Japan. We also examined the association of serum PLTP concentration with other cardiovascular risk factors. Methods SubjectsThe present analysis is based on a cohort of male workers in a worksite in Aichi prefecture, central Japan. 18,19 Its aim was to determine factors associated with the development of cardiovascular diseases. The study began in 1997, when 2,896 male employees of a manufacturing company, aged 34-59 years, were recruited as potential participants. A self-administered questionnaire was used to assess the

Serum, but not monocyte macrophage foam cells derived from low HDL-C subjects, displays reduced cholesterol efflux capacity

“…Phospholipid transfer activity of PLTP has been associated with various pathophysiological conditions; however, little information is available concerning the relationship between PLTP mass and disease. Interestingly, an inverse relationship between serum total PLTP concentration and CHD risk was recently reported (54). However, the physiological role of LA-PLTP remains unknown.…”

A point mutant of apolipoprotein A-I, V156K, exhibited potent anti-oxidant and anti-atherosclerotic activity in hypercholesterolemic C57BL/6 mice

“…Serum PLTP performs crucial functions in HDL remodeling and the maintenance of HDL levels via the transfer of phospholipids from remnant lipoproteins. The relationship between PLTP and CHD remains a matter of some controversy, i.e., high PLTP activity has been identified as a risk factor for CHD (Schlitt et al, 2003) but PLTP mass also appears to be a protective factor against CHD (Yatsuya et al, 2004). A study of 1,102 CHD patients indicated that the concentration of serum PLTP was significantly inversely related with the risk of cardiovascular disease (Yatsuya et al, 2004).…”

“…The relationship between PLTP and CHD remains a matter of some controversy, i.e., high PLTP activity has been identified as a risk factor for CHD (Schlitt et al, 2003) but PLTP mass also appears to be a protective factor against CHD (Yatsuya et al, 2004). A study of 1,102 CHD patients indicated that the concentration of serum PLTP was significantly inversely related with the risk of cardiovascular disease (Yatsuya et al, 2004). This finding shows that immuno-detected PLTP masses increased in cases of V156K-rHDL or R173C-rHDL injection, thereby suggesting that increases in PLTP mass might be correlated with anti-atherosclerotic processes.…”

Plasma phospholipid transfer activity is essential for increased atherogenesis in PLTP transgenic mice: a mutation-inactivation study

“…The role of this low-active PLTP, however, is not well understood. In a Japanese cohort study, a possible protective role for serum PLTP mass in coronary heart disease was indicated, independent of PLTP activity (25). Recently, it was published that distribution of PLTP between high-activity and low-activity forms may be disturbed in peripheral arterial disease (26).…”