Associations of Biomarkers of Kidney Tubule Health with Retinal Microvascular Signs: The Multi-Ethnic Study of Atherosclerosis (MESA).

Background: CKD is strongly associated with cardiovascular disease (CVD), yet the etiology responsible for this link remains elusive. Novel blood and urine biomarkers reflecting kidney tubule dysfunction and injury may provide novel insights to mechanisms linking the kidney to CVD.

Methods: In 470 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) without type 2 diabetes, CVD or CKD, we measured six plasma (kidney injury molecule-1 [KIM-1], monocyte chemoattractant protein-1 [MCP-1], soluble urokinase plasminogen activator receptor [suPAR], tumor necrosis factor receptor [TNFR] 1 and 2, and anti-chitinase-3-like protein 1 [YKL-40]) and six urinary (alpha 1 microglobulin [A-1M], epidermal growth factor [EGF], KIM-1, MCP-1, YKL-40 and uromodulin [UMOD]) kidney tubule health biomarkers.

Microvascular dysfunction across organs in heart failure with preserved ejection fraction: the PROSE-HFpEF case-control study.

Background: Systemic microvascular dysfunction is proposed as a key pathophysiological process in heart failure with preserved ejection fraction (HFpEF). This study compared microvasculature across vascular beds in HFpEF patients and controls.

Methods: This prospective, case-control study included subjects ≥ 60years.

Steatotic liver disease interacts with a polygenic risk score for triglyceride clearance to impact the risk of hypertriglyceridaemia: The Maastricht Study.

Aims/hypothesis: The pathogenesis of hypertriglyceridaemia is explained by a complex interplay between genetic and environmental factors. We hypothesised that intrahepatic lipid (IHL) content, which drives the production of triacylglycerol-rich VLDL particles, interacts with a polygenic risk score (PRS) for triglyceride clearance to impact the risk of hypertriglyceridaemia.

Methods: We used data from The Maastricht Study, a population-based prospective cohort study (n=3810; age: 60 years, 48% women, 10% hypertriglyceridaemia, 26% steatotic liver disease).

Type 2 diabetes and depression via microvascular dysfunction, neurodegeneration, inflammation, advanced glycation end products (AGEs), and arterial stiffness.

Aims: Type 2 diabetes increases the risk of depression, but the mechanisms underlying this association are incompletely understood. We investigated whether microvascular dysfunction, neurodegeneration, low-grade inflammation, advanced glycation end products (AGEs) and arterial stiffness, pathologies that are more common in diabetes, explain, or mediate the association between type 2 diabetes and incident clinically relevant depressive symptoms.

Materials And Methods: We used prospective data from The Maastricht Study, a population-based cohort study.

Aerobic Exercise Preconditioning Does Not Augment Muscle Hypertrophy During Subsequent Resistance Exercise Training in Healthy Older Adults.

Background: Resistance exercise training is an effective treatment strategy to counteract the age-related loss of muscle mass and strength in older adults. However, there is a large inter-individual variation in muscle fiber hypertrophy following resistance exercise training. It has been hypothesized that a less than optimal muscle fiber capillarization and perfusion capacity may compromise muscle hypertrophy during resistance exercise training in older adults.

Postexercise Cooling Lowers Skeletal Muscle Microvascular Perfusion and Blunts Amino Acid Incorporation into Muscle Tissue in Active Young Adults.

Purpose: Cold-water immersion lowers muscle protein synthesis rates during postexercise recovery. Whether this effect can be explained by lower muscle microvascular perfusion and a subsequent decline in postprandial amino acid incorporation into muscle tissue after cooling is currently unknown.

Methods: Twelve young males (24 ± 4 yr) performed a single resistance exercise session followed by water immersion for 20 min with one leg immersed in cold water (8°C: COLD) and the contralateral leg in thermoneutral water (30°C: CON).

Fructose restriction has beneficial effects on adipose tissue distribution but not on serum adipokine levels: Post-hoc analysis of a double-blind randomized controlled trial.

We aimed to examine the effects of isocaloric fructose restriction on adipose tissue distribution and serum adipokines. Individuals with BMI >28 kg/m (n = 44) followed a 6-week fructose-restricted diet and were randomly allocated to (double-blind) oral supplementation with fructose (control) or glucose (intervention) powder three times daily. Visceral (VAT) and subcutaneous (SAT) adipose tissue was quantified with MRI.

Retinal microvascular function and incidence and trajectories of clinically relevant depressive symptoms: the Maastricht Study.

Background: Cerebral microvascular dysfunction may contribute to depression via disruption of brain structures involved in mood regulation, but evidence is limited. We investigated the association of retinal microvascular function, a proxy for microvascular function in the brain, with incidence and trajectories of clinically relevant depressive symptoms.

Methods: Longitudinal data are from The Maastricht Study of 5952 participants (59.

Microvascular Dysfunction and Whole-Brain White Matter Connectivity: The Maastricht Study.

Background: Microvascular dysfunction is involved in the development of various cerebral disorders. It may contribute to these disorders by disrupting white matter tracts and altering brain connectivity, but evidence is scarce. We investigated the association between multiple biomarkers of microvascular function and whole-brain white matter connectivity.

Type II Muscle Fiber Capillarization Is an Important Determinant of Post-Exercise Microvascular Perfusion in Older Adults.

Introduction: Microvascular perfusion is essential for post-exercise skeletal muscle recovery to ensure adequate delivery of nutrients and growth factors. This study assessed the relationship between various indices of muscle fiber capillarization and microvascular perfusion assessed by contrast-enhanced ultrasound (CEUS) at rest and during recovery from a bout of resistance exercise in older adults.

Methods: Sixteen older adults (72 ± 6 y, 5/11 male/female) participated in an experimental test day during which a muscle biopsy was collected from the vastus lateralis and microvascular perfusion was determined by CEUS at rest and at 10 and 40 min following a bout of resistance exercise.

Capillary rarefaction: a missing link in renal and cardiovascular disease?

Patients with chronic kidney disease (CKD) have an increased risk for cardiovascular morbidity and mortality. Capillary rarefaction may be both one of the causes as well as a consequence of CKD and cardiovascular disease. We reviewed the published literature on human biopsy studies and conclude that renal capillary rarefaction occurs independently of the cause of renal function decline.

Habitual intake of advanced glycation endproducts is not associated with worse insulin sensitivity, worse beta cell function, or presence of prediabetes or type 2 diabetes: The Maastricht Study.

Background & Aims: A diet high in advanced glycation endproducts (AGEs) is a potential risk factor for insulin resistance, beta cell dysfunction, and ultimately type 2 diabetes. We investigated associations between habitual intake of dietary AGEs and glucose metabolism in a population-based setting.

Methods: In 6275 participants of The Maastricht Study (mean ± SD age: 60 ± 9, 15.

Alcohol consumption and microvascular dysfunction: a J-shaped association: The Maastricht Study.

Background: Microvascular dysfunction (MVD) is an important contributor to major clinical disease such as stroke, dementia, depression, retinopathy, and chronic kidney disease. Alcohol consumption may be a determinant of MVD.

Objective: Main objectives were (1) to study whether alcohol consumption was associated with MVD as assessed in the brain, retina, skin, kidney and in the blood; and (2) to investigate whether associations differed by history of cardiovascular disease or sex.

Pyridoxamine reduces methylglyoxal and markers of glycation and endothelial dysfunction, but does not improve insulin sensitivity or vascular function in abdominally obese individuals: A randomized double-blind placebo-controlled trial.

Aim: To investigate the effects of pyridoxamine (PM), a B6 vitamer and dicarbonyl scavenger, on glycation and a large panel of metabolic and vascular measurements in a randomized double-blind placebo-controlled trial in abdominally obese individuals.

Materials And Methods: Individuals (54% female; mean age 50 years; mean body mass index 32 kg/m ) were randomized to an 8-week intervention with either placebo (n = 36), 25 mg PM (n = 36) or 200 mg PM (n = 36). We assessed insulin sensitivity, β-cell function, insulin-mediated microvascular recruitment, skin microvascular function, flow-mediated dilation, and plasma inflammation and endothelial function markers.

Habitual intake of dietary methylglyoxal is associated with less low-grade inflammation: the Maastricht Study.

Background: Dicarbonyls are major reactive precursors of advanced glycation endproducts (AGEs). Dicarbonyls are formed endogenously and also during food processing. Circulating dicarbonyls and AGEs are associated with inflammation and microvascular complications of diabetes, but for dicarbonyls from the diet these associations are currently unknown.

Retinal microvascular function is associated with the cerebral microcirculation as determined by intravoxel incoherent motion MRI.

Background And Aims: The easily accessible retinal vessels provide a unique opportunity to study a proxy for cerebral small vessels. Associations between retinal vessel diameters and macrostructural brain white matter changes have already been demonstrated. Alterations in microvascular function, likely precede these structural abnormalities.

A randomized diet-induced weight-loss intervention reduces plasma complement C3: Possible implication for endothelial dysfunction.

Objective: Complement C3 and other components of the alternative pathway are higher in individuals with obesity. Moreover, C3 has been identified as a risk factor for cardiovascular disease. This study investigated whether, and how, a weight-loss intervention reduced plasma C3, activated C3 (C3a), and factor D and explored potential biological effects of such a reduction.

A 4-Week Diet Low or High in Advanced Glycation Endproducts Has Limited Impact on Gut Microbial Composition in Abdominally Obese Individuals: The deAGEing Trial.

Dietary advanced glycation endproducts (AGEs), abundantly present in Westernized diets, are linked to negative health outcomes, but their impact on the gut microbiota has not yet been well investigated in humans. We investigated the effects of a 4-week isocaloric and macronutrient-matched diet low or high in AGEs on the gut microbial composition of 70 abdominally obese individuals in a double-blind parallel-design randomized controlled trial (NCT03866343). Additionally, we investigated the cross-sectional associations between the habitual intake of dietary dicarbonyls, reactive precursors to AGEs, and the gut microbial composition, as assessed by 16S rRNA amplicon-based sequencing.

Effects of Diet-Induced Weight Loss on Plasma Markers for Cholesterol Absorption and Synthesis: Secondary Analysis of a Randomized Trial in Abdominally Obese Men.

Cross-sectional studies have shown that obesity is associated with lower intestinal cholesterol absorption and higher endogenous cholesterol synthesis. These metabolic characteristics have also been observed in patients with type 2 diabetes, metabolic syndrome, steatosis or cholestasis. The number of intervention studies evaluating the effect of weight loss on these metabolic characteristics is, however, limited, while the role of the different fat compartments has not been studied into detail.

Renal Clearance of Fibroblast Growth Factor-23 (FGF23) and its Fragments in Humans.

Relative abundance of fibroblast growth factor-23 (FGF23) measured by the C-terminal (cFGF23, which measures both intact FGF23 and C-terminal fragments) versus intact (iFGF23, measures only intact hormone) assays varies by kidney function in humans. Differential kidney clearance may explain this finding. We measured cFGF23 and iFGF23 in the aorta and bilateral renal veins of 162 patients with essential hypertension undergoing renal angiography.