Age-Related Progression of Microvascular Dysfunction in Cystic Fibrosis: New Detection Ways and Clinical Outcomes

There are concerns about altered vascular functions that could play an important role in the pathogenesis and influence the severity of chronic disease, however, increased cardiovascular risk in paediatric cystic fibrosis (CF) has not been yet fully understood. Aim was to analyse vascular disease risk and investigate changes over times in CF and controls. We prospectively enrolled 22 CF subjects (a median age of 16.07 years), and 22 healthy demographically matched controls (a median age of 17.28 years) and determined endothelial function. We utilised a combined diagnostic approach by measuring the plethysmographic Reactive Hyperemia Index (RHI) as the post-to preocclusive endothelium-dependent changes of vascular tone, and biomarkers that are known to be related to endothelial dysfunction (ED): asymmetric dimethyl arginine (ADMA), high-sensitive CRP (hsCRP), VCAM-1 and E-selectin. RHI values were significantly lower in CF young adults (p<0.005). HsCRP (p<0.005), E-selectin (p<0.001) and VCAM-1 (p<0.001) were significantly increased in CF patients since childhood. The findings have provided a detailed account of the ongoing process of microvascular dysfunction with gradual progression with the age of CF patients, making them further at risk of advanced vascular disease. Elevations of biomarkers in CF children with not yet demonstrated RHI changes but with significantly reduced RHI in adulthood and lipid profile changes indicate the possible occurrence of ED with CF-related specific risk factors over time and will enable us to provide the best possible support.

Download Full-text

Evidence of microvascular dysfunction in patients with cystic fibrosis

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00136.2016 ◽

2016 ◽

Vol 310 (11) ◽

pp. H1479-H1485 ◽

Cited By ~ 20

Author(s):

Paula Rodriguez-Miguelez ◽

Jeffrey Thomas ◽

Nichole Seigler ◽

Reva Crandall ◽

Kathleen T. McKie ◽

...

Keyword(s):

Cystic Fibrosis ◽

Exercise Capacity ◽

Reactive Hyperemia ◽

Clinical Manifestations ◽

Microvascular Dysfunction ◽

Forced Expiratory Volume ◽

Microvascular Function ◽

Doppler Imaging ◽

Control Subjects ◽

Positive Correlations

Cystic fibrosis (CF) is a genetic, multisystemic disorder with broad clinical manifestations apart from the well-characterized pulmonary dysfunction. Recent findings have described impairment in conduit vessel function in patients with CF; however, whether microvascular function is affected in this population has yet to be elucidated. Using laser-Doppler imaging, we evaluated microvascular function through postocclusive reactive hyperemia (PORH), local thermal hyperemia (LTH), and iontophoresis with acetylcholine (ACh). PORH [518 ± 174% (CF) and 801 ± 125% (control), P = 0.039], LTH [1,338 ± 436% (CF) and 1,574 ± 620% (control), P = 0.045], and iontophoresis with ACh [416 ± 140% (CF) and 617 ± 143% (control), P = 0.032] were significantly lower in patients with CF than control subjects. In addition, the ratio of PORH to LTH was significantly ( P = 0.043) lower in patients with CF (55.3 ± 5.1%) than control subjects (68.8 ± 3.1%). Significant positive correlations between LTH and forced expiratory volume in 1 s (%predicted) ( r = 0.441, P = 0.013) and between the PORH-to-LTH ratio and exercise capacity ( r = 0.350, P = 0.049) were observed. These data provide evidence of microvascular dysfunction in patients with CF compared with control subjects. In addition, our data demonstrate a complex relationship between microvascular function and classical markers of disease severity (i.e., pulmonary function and exercise capacity) in CF.

Download Full-text

Hyper-Coagulable Profile with Elevated Pro-Thrombotic Biomarkers and Increased Cerebro- and Cardio-Vascular Disease Risk Exist Among Healthy Dyslipidemic Women

Current Neurovascular Research ◽

10.2174/1567202611666140307104724 ◽

2014 ◽

Vol 11 (2) ◽

pp. 142-148 ◽

Cited By ~ 1

Author(s):

Claudia Ferreira ◽

Maria Carvalho ◽

Helton Reis ◽

Karina Gomes ◽

Marinez Sousa ◽

...

Keyword(s):

Vascular Disease ◽

Disease Risk ◽

Cardio Vascular Disease ◽

Cardio Vascular

Download Full-text

Adipose Tissue and Bone Marrow as Sources for Cell-based Therapeutic Angiogenesis in Ischemic Tissues: Biological Foundation and Clinical Prospects for Age-related Vascular Disease

Immunology Endocrine & Metabolic Agents - Medicinal Chemistry ◽

10.2174/1871522215666150910210441 ◽

2015 ◽

Vol 15 (2) ◽

pp. 145-159

Author(s):

Dmitry Bulgin ◽

Enes Hodzic

Keyword(s):

Bone Marrow ◽

Adipose Tissue ◽

Vascular Disease ◽

Therapeutic Angiogenesis ◽

Age Related ◽

Biological Foundation

Download Full-text

The TOMM40 ‘523’ polymorphism in disease risk and age of symptom onset in two independent cohorts of Parkinson’s disease

Scientific Reports ◽

10.1038/s41598-021-85510-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Megan C. Bakeberg ◽

Madison E. Hoes ◽

Anastazja M. Gorecki ◽

Frances Theunissen ◽

Abigail L. Pfaff ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Symptom Onset ◽

Disease Risk ◽

Age Of Onset ◽

Sequencing Analysis ◽

Age Related ◽

Australian Cohort ◽

Progression Markers ◽

Age Related Cognitive Decline

AbstractAbnormal mitochondrial function is a key process in the pathogenesis of Parkinson’s disease (PD). The central pore-forming protein TOM40 of the mitochondria is encoded by the translocase of outer mitochondrial membrane 40 homologue gene (TOMM40). The highly variant ‘523’ poly-T repeat is associated with age-related cognitive decline and age of onset in Alzheimer’s disease, but whether it plays a role in modifying the risk or clinical course of PD it yet to be elucidated. The TOMM40 ‘523’ allele length was determined in 634 people with PD and 422 healthy controls from an Australian cohort and the Parkinson’s Progression Markers Initiative (PPMI) cohort, using polymerase chain reaction or whole genome sequencing analysis. Genotype and allele frequencies of TOMM40 ‘523’ and APOE ε did not differ significantly between the cohorts. Analyses revealed TOMM40 ‘523’ allele groups were not associated with disease risk, while considering APOE ε genotype. Regression analyses revealed the TOMM40 S/S genotype was associated with a significantly later age of symptom onset in the PPMI PD cohort, but not after correction for covariates, or in the Australian cohort. Whilst variation in the TOMM40 ‘523’ polymorphism was not associated with PD risk, the possibility that it may be a modifying factor for age of symptom onset warrants further investigation in other PD populations.

Download Full-text

Bone Morphogenetic Proteins and Diabetic Retinopathy

Biomolecules ◽

10.3390/biom11040593 ◽

2021 ◽

Vol 11 (4) ◽

pp. 593

Author(s):

Khaled Elmasry ◽

Samar Habib ◽

Mohamed Moustafa ◽

Mohamed Al-Shabrawey

Keyword(s):

Diabetic Retinopathy ◽

Bone Morphogenetic Proteins ◽

Potential Role ◽

Microvascular Dysfunction ◽

Cardiovascular Complications ◽

Bmp Signaling ◽

Age Related Macular Degeneration ◽

Age Related ◽

Retinal Inflammation ◽

Underlying Mechanisms

Bone morphogenetic proteins (BMPs) play an important role in bone formation and repair. Recent studies underscored their essential role in the normal development of several organs and vascular homeostasis in health and diseases. Elevated levels of BMPs have been linked to the development of cardiovascular complications of diabetes mellitus. However, their particular role in the pathogenesis of microvascular dysfunction associated with diabetic retinopathy (DR) is still under-investigated. Accumulated evidence from our and others’ studies suggests the involvement of BMP signaling in retinal inflammation, hyperpermeability and pathological neovascularization in DR and age-related macular degeneration (AMD). Therefore, targeting BMP signaling in diabetes is proposed as a potential therapeutic strategy to halt the development of microvascular dysfunction in retinal diseases, particularly in DR. The goal of this review article is to discuss the biological functions of BMPs, their underlying mechanisms and their potential role in the pathogenesis of DR in particular.

Download Full-text

RAGE, vascular tone and vascular disease

Pharmacology & Therapeutics ◽

10.1016/j.pharmthera.2009.06.013 ◽

2009 ◽

Vol 124 (2) ◽

pp. 185-194 ◽

Cited By ~ 64

Author(s):

David G.S. Farmer ◽

Simon Kennedy

Keyword(s):

Vascular Disease ◽

Vascular Tone

Download Full-text

Vascular disease/risk and late-life depression in a Korean community population

The British Journal of Psychiatry ◽

10.1192/bjp.185.2.102 ◽

2004 ◽

Vol 185 (2) ◽

pp. 102-107 ◽

Cited By ~ 43

Author(s):

Jae-Min Kim ◽

Robert Stewart ◽

Il-Seon Shin ◽

Jin-Sang Yoon

Keyword(s):

Risk Factors ◽

Cognitive Function ◽

Vascular Disease ◽

Disease Risk ◽

Apoe Genotype ◽

Density Lipoprotein ◽

Late Life ◽

Late Life Depression ◽

Previous Stroke ◽

Community Population

BackgroundAssociations between vascular risk factors and late-life depression are controversial.AimsTo investigate the association between measures of vascular disease/ risk and depression and confounding and effect modification by APOE genotype and cognitive function.MethodIn a Korean community population aged 65+ (n=732), diagnosis of depression (Geriatric Mental State Schedule) and information on vascular status, disability, APOE genotype and cognitive function were obtained.ResultsPrevious stroke and lower high-density lipoprotein cholesterol level (but neither hypertension nor diabetes) were significantly associated with depression (independently of disability and cognitive function). These associations were stronger in participants with borderline cognitive impairment, although not to a significant extent.ConclusionsExcept for previous stroke and an atherogenic lipid profile, associations between depression and other common risk factors for cerebrovascular disease were not evident.

Download Full-text