The role of plasma phospholipid transfer protein (PLTP) in the development of atherosclerosis : studies in genetically modified mice

Complications of atherosclerosis are the principal cause of mortality in Western societies. Epidemiological studies have shown that a high HDL cholesterol level in plasma is inversely correlated with the risk for atherosclerosis. The exact biological mechanism behind this finding is not known. There are many factors that affect HDL metabolism. In vitro and in vivo studies demonstrated that plasma phospholipid transfer protein (PLTP) plays a major role in phospholipid transfer processes between lipoproteins, and also in modulating size and composition of HDL particles. The aim of this thesis was to clarify the role of PLTP in HDL metabolism and in the development of atherosclerosis. Normal mice lack cholesteryl ester transfer protein (CETP) and have very low LDL plasma levels compared with humans. Therefore we used a genetically modified mouse model with a humanlike lipoprotein profile. These animals are transgenic for CETP and carry one mutated allele of the LDL receptor (huCETPtg/LDL-R+I-)

Studi Literatur Digitalisasi Model 5A untuk Pengendalian Obesitas Saat Pandemi COVID-19

The COVID-19 pandemic has had an impact on health regulations made by WHO and the Indonesian Ministry of Health. Recent studies have shown a significant association with self-isolation and behavioral changes such as decreased physical activity and decreased diet with risk of obesity. The existence of social media and mobile apps as a medium of communication can help change lifestyle behaviors and unhealthy diet patterns. The purpose of study was to collect and analize healthcare digitalization articles especially obesity management and 5A model. The study method was literature review. Fulltext Articles was collected from google scholar and pubmed with some keywords such as obesity, epidemiology, COVID-19, pandemic, technology, communication, education, promotion, prevention. The result stated that the digitalization of obesity management with social media and machine learning mobile app could increase patients independence to improve their weight such as behaviour change, lifestyle and dietary pattern

Vitamin D-Binding Protein Polymorphisms, 25-Hydroxyvitamin D, Sunshine and Multiple Sclerosis

Blacks have different dominant polymorphisms in the vitamin D-binding protein (DBP) gene that result in higher bioavailable vitamin D than whites. This study tested whether the lack of association between 25-hydroxyvitamin D (25OHD) and multiple sclerosis (MS) risk in blacks and Hispanics is due to differences in these common polymorphisms (rs7041, rs4588). We recruited incident MS cases and controls (blacks 116 cases/131 controls; Hispanics 183/197; whites 247/267) from Kaiser Permanente Southern California. AA is the dominant rs7041 genotype in blacks (70.0%) whereas C is the dominant allele in whites (79.0% AC/CC) and Hispanics (77.1%). Higher 25OHD levels were associated with a lower risk of MS in whites who carried at least one copy of the C allele but not AA carriers. No association was found in Hispanics or blacks regardless of genotype. Higher ultraviolet radiation exposure was associated with a lower risk of MS in blacks (OR = 0.06), Hispanics and whites who carried at least one copy of the C allele but not in others. Racial/ethnic variations in bioavailable vitamin D do not explain the lack of association between 25OHD and MS in blacks and Hispanics. These findings further challenge the biological plausibility of vitamin D deficiency as causal for MS

MS Sunshine Study: Sun Exposure But Not Vitamin D Is Associated with Multiple Sclerosis Risk in Blacks and Hispanics

Multiple sclerosis (MS) incidence and serum 25-hydroxyvitamin D (25OHD) levels vary by race/ethnicity. We examined the consistency of beneficial effects of 25OHD and/or sun exposure for MS risk across multiple racial/ethnic groups. We recruited incident MS cases and controls (blacks 116 cases/131 controls; Hispanics 183/197; whites 247/267) from the membership of Kaiser Permanente Southern California into the MS Sunshine Study to simultaneously examine sun exposure and 25OHD, accounting for genetic ancestry and other factors. Higher lifetime ultraviolet radiation exposure (a rigorous measure of sun exposure) was associated with a lower risk of MS independent of serum 25OHD levels in blacks (adjusted OR = 0.53, 95% CI = 0.31-0.83; p = 0.007) and whites (OR = 0.68, 95% CI = 0.48-0.94; p = 0.020) with a similar magnitude of effect that did not reach statistical significance in Hispanics (OR = 0.66, 95% CI = 0.42-1.04; p = 0.071). Higher serum 25OHD levels were associated with a lower risk of MS only in whites. No association was found in Hispanics or blacks regardless of how 25OHD was modeled. Lifetime sun exposure appears to reduce the risk of MS regardless of race/ethnicity. In contrast, serum 25OHD levels are not associated with MS risk in blacks or Hispanics. Our findings challenge the biological plausibility of vitamin D deficiency as causal for MS and call into question the targeting of specific serum 25OHD levels to achieve health benefits, particularly in blacks and Hispanics

Elevation of plasma phospholipid transfer protein in transgenic mice increases VLDL secretion

Two lipid transfer proteins are active in human plasma, cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP). Mice by nature do not express CETP. Additional inactivation of the PLTP gene resulted in reduced secretion of VLDL and subsequently in decreased susceptibility to diet-induced atherosclerosis. The aim of this study is to assess possible effects of differences in PLTP expression on VLDL secretion in mice that are proficient in CETP and PLTP. We compared human CETP transgenic (huCETPtg) mice with mice expressing both human lipid transfer proteins (huCETPtg/huPLTPtg). Plasma cholesterol in huCETPtg mice was 1.5-fold higher compared with huCETPtg/huPLTPtg mice (P < 0.001). This difference was mostly due to a lower HDL level in the huCETPtg/huPLTPtg mice, which subsequently could lead to the somewhat decreased CETP activity and concentration that was found in huCETPtg/huPLTPtg mice (P < 0.05). PLTP activity was 2.8-fold increased in these animals (P < 0.001). The human PLTP concentration was 5 microg/ml. Moderate overexpression of PLTP resulted in a 1.5-fold higher VLDL secretion compared with huCETPtg mice (P < 0.05). The composition of nascent VLDL was similar in both strains. These results indicate that elevated PLTP activity in huCETPtg mice results in an increase in VLDL secretion. In addition, PLTP overexpression decreases plasma HDL cholesterol as well as CETP

Studi Literatur Digitalisasi Model 5A untuk Pengendalian ObesitasSaat Pandemi COVID-19

Pandemi COVID-19 telah berdampak pada peraturan-peraturan kesehatan yang dibuat WHO dan Kemenkes RI. Studi terbaru menunjukkan adanya hubungan yang signifikan terhadap isolasi mandiri dan perubahan perilaku seperti penurunan aktivitas fisik dan penurunan pola makan dengan risiko obesitas. Adanya sosial media dan mobile apps sebagai media komunikasi dapat membantu perubahan perilaku gaya hidup dan pola diet tidak sehat. Penelitian ini bertujuan untuk mengumpulkan dan menganalisa artikel yang berhubungan dengan digitalisasi pelayanan kesehatan terutama pengendalian obesitas dan model 5 A. Metode riset yang digunakan adalah literature review. Artikel didapatkan melalui mesin pencari seperti google scholar dan pubmed dengan kata kunci yaitu “obesity”, “epidemiology”, “COVID-19”, “pandemic”, “teknologi”, “komunikasi”, “edukasi”, “promotif” “preventif” dan dipilih full text. Berdasarkan hasil penelusuran literatur didapatkan bahwa digitalisasi pelatihan pengendalian obesitas menggunakan sosial media dan machine learning mobile app dapat meningkatkan kemandirian pasien dalam pengendalian obesitas seperti perubahan perubahan perilaku, pola hidup, dan pola die

Evaluation of phospholipid transfer protein and cholesteryl ester transfer protein as contributors to the generation of pre beta-high-density lipoproteins

High-density lipoproteins (HDLs) are considered anti-atherogenic because they mediate peripheral cell cholesterol transport to the liver for excretion and degradation. An important step in this reverse cholesterol-transport pathway is the uptake of cellular cholesterol by a specific subclass of small, lipid-poor apolipoprotein A-I particles designated pre beta-HDL. The two lipid-transfer proteins present in human plasma, cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP), have both been implicated in the formation of pre beta-HDL. In order to investigate the relative contribution of each of these proteins, we used transgenic mouse models. Comparisons were made between human CETP transgenic mice (huCETPtg), human PLTP transgenic mice (huPLTPtg) and mice transgenic for both lipid-transfer proteins (huCETPtg/huPLTPtg). These animals showed elevated plasma levels of CETP activity, PLTP activity or both activities, respectively. We evaluated the generation of pre beta-HDL in mouse plasma by immunoblotting and crossed immuno-electrophoresis. Generation of pre beta-HDL was equal in huCETPtg and wild-type mice. In contrast, in huPLTPtg and huCETPtg/huPLTPtg mice, pre beta-HDL generation was 3-fold higher than in plasma from either wild-type or huCETPtg mice. Our findings demonstrate that, of the two plasma lipid-transfer proteins, PLTP rather than CETP is responsible for the generation of pre beta-HDL. These data support the hypothesis of a role for PLTP in the initial stage of reverse cholesterol transport

Elevation of plasma phospholipid transfer protein increases the risk of atherosclerosis despite lower apolipoprotein B-containing lipoproteins.

Plasma phospholipid transfer protein (PLTP) transfers phospholipids between lipoproteins and mediates HDL conversion. PLTP-overexpressing mice have increased atherosclerosis. However, mice do not express cholesteryl ester transfer protein (CETP), which is involved in the same metabolic pathways as PLTP. Therefore, we studied atherosclerosis in heterozygous LDL receptor-deficient (LDLR(+/-)) mice expressing both human CETP and human PLTP. We used two transgenic lines with moderately and highly elevated plasma PLTP activity. In LDLR(+/-)/huCETPtg mice, cholesterol is present in both LDL and HDL. Both are decreased in LDLR(+/-)/huCETPtg/huPLTPtg mice (>50%). An atherogenic diet resulted in high levels of VLDL+LDL cholesterol. PLTP expression caused a strong PLTP dose-dependent decrease in VLDL and LDL cholesterol (-26% and -69%) and a decrease in HDL cholesterol (-70%). Surprisingly, atherosclerosis was increased in the two transgenic lines with moderately and highly elevated plasma PLTP activity (1.9-fold and 4.4-fold, respectively), indicating that the adverse effect of the reduction in plasma HDL outweighs the beneficial effect of the reduction in apolipoprotein B (apoB)-containing lipoproteins. The activities of the antiatherogenic enzymes paraoxonase and platelet-activating factor acetyl hydrolase were both PLTP dose-dependently reduced ( approximately -33% and -65%, respectively). We conclude that expression of PLTP in this animal model results in increased atherosclerosis in spite of reduced apoB-containing lipoproteins, by reduction of HDL and of HDL-associated antioxidant enzyme activities