TY - JOUR A1 - Lehn-Stefan, Angela A1 - Peter, Andreas A1 - Machann, Jürgen A1 - Schick, Fritz A1 - Randrianarisoa, Elko A1 - Heni, Martin A1 - Wagner, Robert A1 - Birkenfeld, Andreas L. A1 - Fritsche, Andreas A1 - Schulze, Matthias Bernd A1 - Stefan, Norbert A1 - Kantartzis, Konstantinos T1 - Impaired metabolic health and low cardiorespiratory fitness independently associate with subclinical atherosclerosis in obesity JF - The journal of clinical endocrinology & metabolism N2 - Context For a given body mass index (BMI), both impaired metabolic health (MH) and reduced cardiorespiratory fitness (CRF) associate with increased risk of cardiovascular disease (CVD). Objective It remains unknown whether both risk phenotypes relate to CVD independently of each other, and whether these relationships differ in normal weight, overweight, and obese subjects. Methods Data from 421 participants from the Tubingen Diabetes Family Study, who had measurements of anthropometrics, metabolic parameters, CRF (maximal aerobic capacity [VO2max]) and carotid intima-media thickness (cIMT), an early marker of atherosclerosis, were analyzed. Subjects were divided by BMI and MH status into 6 phenotypes. Results In univariate analyses, older age, increased BMI, and a metabolic risk profile correlated positively, while insulin sensitivity and VO2max negatively with cIMT. In multivariable analyses in obese subjects, older age, male sex, lower VO2max (std. ss -0.21, P = 0.002) and impaired MH (std. ss 0.13, P = 0.02) were independent determinants of increased cIMT. After adjustment for age and sex, subjects with metabolically healthy obesity (MHO) had higher cIMT than subjects with metabolically healthy normal weight (MHNW; 0.59 +/- 0.009 vs 0.52 +/- 0.01 mm; P < 0.05). When VO2max was additionally included in this model, the difference in cIMT between MHO and MHNW groups became statistically nonsignificant (0.58 +/- 0.009 vs 0.56 +/- 0.02 mm; P > 0.05). Conclusion These data suggest that impaired MH and low CRF independently determine increased cIMT in obese subjects and that low CRF may explain part of the increased CVD risk observed in MHO compared with MHNW. KW - Metabolically healthy obesity KW - cardiorespiratory fitness KW - subclinical KW - atherosclerosis KW - obesity KW - carotid intima-media thickness KW - cardiovascular KW - disease Y1 - 2022 U6 - https://doi.org/10.1210/clinem/dgac091 SN - 0021-972X SN - 1945-7197 VL - 107 IS - 6 SP - E2417 EP - E2424 PB - Endocrine Society CY - Washington ER - TY - JOUR A1 - Prüfer, Nicole A1 - Kleuser, Burkhard A1 - van der Giet, Markus T1 - The role of serum amyloid A and sphingosine-1-phosphate on high-density lipoprotein functionality JF - Biological chemistry N2 - The high-density lipoprotein (HDL) is one of the most important endogenous cardiovascular protective markers. HDL is an attractive target in the search for new pharmaceutical therapies and in the prevention of cardiovascular events. Some of HDL's anti-atherogenic properties are related to the signaling molecule sphingosine-1-phosphate (S1P), which plays an important role in vascular homeostasis. However, for different patient populations it seems more complicated. Significant changes in HDL's protective potency are reduced under pathologic conditions and HDL might even serve as a proatherogenic particle. Under uremic conditions especially there is a change in the compounds associated with HDL. S1P is reduced and acute phase proteins such as serum amyloid A (SAA) are found to be elevated in HDL. The conversion of HDL in inflammation changes the functional properties of HDL. High amounts of SAA are associated with the occurrence of cardiovascular diseases such as atherosclerosis. SAA has potent pro-atherogenic properties, which may have impact on HDL's biological functions, including cholesterol efflux capacity, antioxidative and anti-inflammatory activities. This review focuses on two molecules that affect the functionality of HDL. The balance between functional and dysfunctional HDL is disturbed after the loss of the protective sphingolipid molecule S1P and the accumulation of the acute-phase protein SAA. This review also summarizes the biological activities of lipid-free and lipid-bound SAA and its impact on HDL function. KW - atherosclerosis KW - high-density lipoprotein (HDL) KW - inflammation KW - serum amyloid A (SAA) KW - sphingosine-1-phosphate (S1P) Y1 - 2015 U6 - https://doi.org/10.1515/hsz-2014-0192 SN - 1431-6730 SN - 1437-4315 VL - 396 IS - 6-7 SP - 573 EP - 583 PB - De Gruyter CY - Berlin ER - TY - JOUR A1 - Chaykovska, Lyubov A1 - Zientara, Alicja A1 - Reser, Diana A1 - Weise, Alexander A1 - Reichert, Wolfgang A1 - Hocher, Berthold T1 - Development and validation of a macroarray system - MutaCHIP (R) ARTERO - for the detection of genetic variants involved in the pathogenesis of atherosclerosis JF - Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion N2 - Background: Cardiovascular diseases are the leading cause of death in developed countries. The underlying mechanism is often atherosclerotic remodeling of blood vessels in organs such as heart, kidney, brain, and large arteries in case of peripheral arterial disease. Beside environmental and behavioral factors such as smoking or lack of physical activity, genetic variants in genes involved in lipid metabolism, blood pressure regulation, oxidative stress, and coagulation play a prominent role in the pathogenesis of atherosclerosis. Methods: Thus, we developed and validated for clinical use and research a macroarray system for the simultaneous detection of key genetic variants in genes involved in lipid metabolism, blood pressure regulation, oxidative stress, and coagulation. Results: When compared with standard PCR technologies to determine all these genetic variants in parallel, the macroarray system (MutaCHIP (R) ARTERO) was as accurate but faster, cheaper, and easier to handle compared to classical real time PCR based technologies. Conclusions: MutaCHIP (R) ARTERO is a gene chip for diagnostics of a complex genetic panel involved in the pathogenesis of atherosclerosis. This method is as sensitive and precise as real time PCR and is able to replicate real time PCR data previously validated in evaluation studies. KW - cardiovascular disease KW - atherosclerosis KW - genes KW - rapid detection method KW - macroarray Y1 - 2014 U6 - https://doi.org/10.7754/Clin.Lab.2014.140104 SN - 1433-6510 VL - 60 IS - 5 SP - 873 EP - 878 PB - Clin Lab Publ., Verl. Klinisches Labor CY - Heidelberg ER -