HDL and LDL: Potential New Players in Breast Cancer Development.

Breast cancer is the most prevalent cancer and primary cause of cancer-related mortality in women. The identification of risk factors can improve prevention of cancer, and obesity and hypercholesterolemia represent potentially modifiable breast cancer risk factors. In the present work, we review the progress to date in research on the potential role of the main cholesterol transporters, low-density and high-density lipoproteins (LDL and HDL), on breast cancer development. Although some studies have failed to find associations between lipoproteins and breast cancer, some large clinical studies have demonstrated a direct association between LDL cholesterol levels and breast cancer risk and an inverse association between HDL cholesterol and breast cancer risk. Research in breast cancer cells and experimental mouse models of breast cancer have demonstrated an important role for cholesterol and its transporters in breast cancer development. Instead of cholesterol, the cholesterol metabolite 27-hydroxycholesterol induces the proliferation of estrogen receptor-positive breast cancer cells and facilitates metastasis. Oxidative modification of the lipoproteins and HDL glycation activate different inflammation-related pathways, thereby enhancing cell proliferation and migration and inhibiting apoptosis. Cholesterol-lowering drugs and apolipoprotein A-I mimetics have emerged as potential therapeutic agents to prevent the deleterious effects of high cholesterol in breast cancer

HDL: A molecular view of the "classic" antiatherogenic lipoprotein

L'estudi del metabolisme de les HDL (lipoproteïnes de densitat alta) i la seva relació amb l'arteriosclerosi és un tema complex, en el qual, recentment, s'han fet avenços importants. Primer, s'ha demostrat que les HDL tenen una acció antiaterogènica. Segon, s'ha establert que aquesta acció és deguda a fraccions que tenen apoA-I però no apoA-II. Tercer, s'han definit alguns mecanismes clau en l'acció antiaterogènica de les HDL: transport invers de colesterol i prevenció de la modificació oxidativa de les LDL (lipoproteïnes de densitat baixa). És previsible que aquests avenços permetran el desenvolupament d'estratègies efectives, que complementaran les existents per al tractament i la prevenció de les malalties cardiovasculars aterotrombòtiques.HDL metabolism and its relationship to atherosclerosis is a complex topic, though notable advances have been made. First, HDL clearly has an anti-atherogenic action. Second, this action is due to some fraction/s containing apoA-I but not apoA-II. Third, some of the molecular mechanisms involved in two key anti-atherogenic functions of HDL have been defined: reverse cholesterol transport and prevention of LDL oxidative modification. These advances may permit the development of effective strategies, complementing those already available, for treating and preventing atherothrombotic cardiovascular diseases

(r)HDL in theranostics : How do we apply HDL's biology for precision medicine in atherosclerosis management?

Altres ajuts: Eusko Jaurlaritza IT-1264-19Altres ajuts: Euskal Herriko UnibertsitateaAltres ajuts: Fondo Europeo de Desarrollo Regional (FEDER)High-density lipoproteins (HDL) are key players in cholesterol metabolism homeostasis since they are responsible for transporting excess cholesterol from peripheral tissues to the liver. Imbalance in this process, due to either excessive accumulation or impaired clearance, results in net cholesterol accumulation and increases the risk of cardiovascular disease (CVD). Therefore, significant effort has been focused on the development of therapeutic tools capable of either directly or indirectly enhancing HDL-guided reverse cholesterol transport (RCT). More recently, in light of the emergence of precision nanomedicine, there has been renewed research interest in attempting to take advantage of the development of advanced recombinant HDL (rHDL) for both therapeutic and diagnostic purposes. In this review, we provide an update on the different approaches that have been developed using rHDL, focusing on the rHDL production methodology and rHDL applications in theranostics. We also compile a series of examples highlighting potential future perspectives in the field

(r)HDL in Theranostics: How Do We Apply HDL's Biology for Precision Medicine in Atherosclerosis Management?

High-density lipoproteins (HDL) are key players in cholesterol metabolism homeostasis since they are responsible for transporting excess cholesterol from peripheral tissues to the liver. Imbalance in this process, due to either excessive accumulation or impaired clearance, results in net cholesterol accumulation and increases the risk of cardiovascular disease (CVD). Therefore, significant effort has been focused on the development of therapeutic tools capable of either directly or indirectly enhancing HDL-guided reverse cholesterol transport (RCT). More recently, in light of the emergence of precision nanomedicine, there has been renewed research interest in attempting to take advantage of the development of advanced recombinant HDL (rHDL) for both therapeutic and diagnostic purposes. In this review, we provide an update on the different approaches that have been developed using rHDL, focusing on the rHDL production methodology and rHDL applications in theranostics. We also compile a series of examples highlighting potential future perspectives in the field.This review was funded by Ministerio de Ciencia, Innovacion y Universidades (PID2019-104367RB-100), as well as the Subprograma Ramon y Cajal (RYC-201722879) to N.R. and PI18/0164 to F.B.-V., FEDER "Una manera de hacer Europa". CIBER de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM) is a project of Instituto de Salud Carlos III. Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau is accredited by the Generalitat de Catalunya as Centre de Recerca de Catalunya (CERCA). This work was also supported by the Basque Government (Grupos Consolidados IT-1264-19) to C.M. and A.B.-V. was supported by Programa de especializacion de Personal Investigador Doctor en la UPV/EHU (2019) 2019-2020

Effect of Whole-Body Vibration Exercise on Balance in Women with Fibromyalgia Syndrome: A Randomized Controlled Trial

Objectives: This study evaluated the effectiveness of a 6-week ‘‘usual care’’ exercise program supplemented with whole-body vibration (WBV) to improve balance and strength in women with fibromyalgia (FM). Design: This was a randomized controlled study. Settings: The setting was a physical therapy department in an academic setting. Subjects: The subjects were 30 postmenopausal women with FM (age: 59 – 7.90 years). Interventions: Subjects were randomized into one of two groups: an experimental group (EG: n = 15), which combined exercise training (2 days a week) with 3 days of WBV, and a control group (CG: n = 15), who performed the same exercise training program (2 days a week) but without WBV. Outcome measures: Balance and muscle strength were measured at baseline and after the 6-week intervention. Results: Significant differences were found ( p < 0.05) between the study groups for the Medio–Lateral Stability Index (MLSI), when patients were assessed with their eyes open and closed. The effect size of the improvement was large with eyes closed (R2 = 0.260) and moderate when the eyes were open (R2 = 0.047). However, no significant differences were found ( p > 0.05) between the study groups for other outcomes. Conclusions: Women with FM may increase their MLSI by engaging in a 6-week traditional exercise program with supplementary WBV. This may have implications for falls prevention in this patient group

Changes in body balance and functional performance following whole-body vibration training in patients withfibromyalgia syndrome: a randomized controlled trial.

Objective: To determine whether an 8-week exercise pro-gramme supplemented with whole-body vibration improves body balance and dynamic strength in women with fibro-myalgia. Design: Randomized controlled trial. Patients: Forty-six participants diagnosed with fibromyal-gia. Methods: Participants were randomly assigned to: (i) an exercise training group with whole-body vibration (n=15), which performed twice-weekly exercise sessions (aerobic ex-ercise, strengthening and flexibility) combined with 3 whole-body vibration training sessions a week (bilateral squats: 6–9 sets of 30 s with 45-s recovery between sets; and uni-lateral squat: 4–7 sets of 30 s, 30 Hz–4 mm); (ii) an exercise group (n=15) with the same combined exercise therapy; and (iii) a usual-care control group (n=16). Results: Statistically significant improvements in the Medio–Lateral Stability Index and Medio–Lateral Mean Deflection with open eyes were found in the whole-body vibration exer-cise group compared with the control group. Non-significant effects were found for lower-limb physical function. Conclusion: The results show that a traditional exercise pro-gramme, supplemented with whole-body vibration training, improved balance in women with fibromyalgia. This may represent a key factor for falls prevention in this patient grou

ApoA-I mimetic administration, but not increased apoA-I-containing HDL, inhibits tumour growth in a mouse model of inherited breast cancer

Low levels of high-density lipoprotein cholesterol (HDLc) have been associated with breast cancer risk, but several epidemiologic studies have reported contradictory results with regard to the relationship between apolipoprotein (apo) A-I and breast cancer. We aimed to determine the effects of human apoA-I overexpression and administration of specific apoA-I mimetic peptide (D-4F) on tumour progression by using mammary tumour virus-polyoma middle T-antigen transgenic (PyMT) mice as a model of inherited breast cancer. Expression of human apoA-I in the mice did not affect tumour onset and growth in PyMT transgenic mice, despite an increase in the HDLc level. In contrast, D-4F treatment significantly increased tumour latency and inhibited the development of tumours. The effects of D-4F on tumour development were independent of 27-hydroxycholesterol. However, D-4F treatment reduced the plasma oxidized low-density lipoprotein (oxLDL) levels in mice and prevented oxLDL-mediated proliferative response in human breast adenocarcinoma MCF-7 cells. In conclusion, our study shows that D-4F, but not apoA-I-containing HDL, hinders tumour growth in mice with inherited breast cancer in association with a higher protection against LDL oxidative modification.This work was partly funded by Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III: FIS PI11/01076 (to F.V-B.), PI12/00291 (to J.C.E-G.) and PI13/02507 (to A.C.), and RETIC RIC RD12/0042/0055 (to A.C.); by Ministerio de Economía y Competitividad, SAF2011-23402 (to A.F.V); by an intramural project of the Institut de Recerca de l’Hospital de la Santa Creu I Sant Pau (IR15-P5); and by grant from the Academy of Finland #257545 (to M.J.). CIBER de Diabetes y Enfermedades Metabólicas Asociadas is an Instituto de Salud Carlos III Project. A.M.F. and S.T.R. were funded by HL-30568 and by a Leducq Foundation Network grant, and J.M.C. is an APIF fellowship recipient (Universitat de Barcelona).Peer Reviewe

Macrophage Cholesterol Efflux Downregulation Is Not Associated with Abdominal Aortic Aneurysm (AAA) Progression

Recent studies have raised the possibility of a role for lipoproteins, including high-density lipoprotein cholesterol (HDLc), in abdominal aortic aneurysm (AAA). The study was conducted in plasmas from 39 large size AAA patients (aortic diameter > 50 mm), 81 small/medium size AAA patients (aortic diameter between 30 and 50 mm) and 38 control subjects (aortic diameter 5 mm per year) in patients with small/medium size AAA. Moreover, no correlation was found between MCE capacity and the aneurysm growth rate. A multivariate Cox regression analysis revealed a significant association between lower MCE capacity with the need for surgery in all AAA patients. Nevertheless, the significance was lost when only small/medium size AAA patients were included. Our results suggest that MCE, a major HDL functional activity, is not involved in AAA progression