Retinal Microvasculature as a Model to Study the Manifestations of Hypertension

Cheung, Carol Y.; Ikram, M. Kamran; Sabanayagam, Charumathi; Wong, Tien Yin

doi:10.1161/hypertensionaha.111.189142

Cited by 222 publications

(178 citation statements)

References 124 publications

Supporting

Mentioning

174

Contrasting

Unclassified

Order By: Relevance

“…Vascular injury and remodeling is the common pathological sequelae in hypertension. 31 GAS5 knockdown affected arterial remodeling in hypertension in SHR. Moreover, blood pressure had the same changing trend as that of vascular remodeling on GAS5 knockdown.…”

Section: Discussionmentioning

confidence: 95%

Long Noncoding RNA-GAS5

et al. 2016

View full text Add to dashboard Cite

H ypertension is a risk factor for several systematic diseases, such as stroke, myocardial infarction, coronary artery disease, and heart failure.1 Vascular remodeling contributes to increased peripheral resistance, affecting both the development and complications of hypertension. Vascular remodeling is an active process of structural changes that involves changes in cellular processes, including growth, apoptosis, migration, inflammation, and production of extracellular matrix proteins. Physiological remodeling is an adaptive response in response to hemodynamic changes and ageing. When this process becomes maladaptive, vascular remodeling contributes to end-organ damage in hypertension and its complications.2,3 Thus, a rationale for the regression of vascular remodeling becomes a therapeutic aim for treating hypertension-related vascular diseases.Long noncoding RNAs (lncRNAs) are noncoding transcripts >200 nucleotides in length. They regulate gene expression at transcriptional, post-transcriptional, and translational levels. 4,5 Increasing studies have revealed that lncRNAs regulate many biological processes, including gene expression, dosage compensation, genomic imprinting, and nuclear-cytoplasmic trafficking. 6 LncRNAs play important roles in tissue homeostasis and pathological conditions. 7 In vascular system, endothelial-expressed lncRNAs regulate vessel growth and function, such as metastasis associated lung adenocarcinoma transcript 1, 8 myocardial infarction associated transcript 9 and tyrosine kinase containing immunoglobulin and epidermal growth factor homology domain-1 antisense transcript.10 Smooth muscle-expressed lncRNAs regulate vascular smooth muscle cell (VSMC) proliferation, migration, and phenotypic switching.11,12 Hypertension is usually characterized by abnormal vascular tone, which is regulated by vascular smooth muscle-mediated vessel contraction and endothelium-dependent vessel vasodilation. 13,14 We speculated that lncRNAs might regulate vascular tone via affecting endothelial cell (EC) and VSMC function.lncRNA, growth arrest-specific 5 (GAS5), is widely expressed in adult tissues and over embryonic development. 15GAS5 was originally isolated from NIH 3T3 mouse embryonic fibroblast cells by subtraction hybridization.16 GAS5 plays important roles in several biological processes, including cell growth arrest, cell proliferation, and apoptosis. 17,18 Hypertension is tightly associated with the dysfunction of ECs and VSMCs. We speculated that abnormal GAS5 expression might alter EC and VSMC function, ultimately affecting the development of hypertension. GAS5 is composed of 12 exons, Abstract-Vascular remodeling is an important pathological feature of hypertension, leading to increased vascular resistance and reduced compliance. Endothelial cell (EC) and vascular smooth muscle cell (VSMC) dysfunction is involved in vascular remodeling. Long noncoding RNAs are potential regulators of EC and VSMC function. Herein, we determined whether long noncoding RNA-growth arrest-specific 5 (GAS5) is invo...

show abstract

Section: Discussionmentioning

confidence: 95%

Long Noncoding RNA-GAS5

et al. 2016

View full text Add to dashboard Cite

show abstract

“…In addition to the well-known association between narrow arteriolar calibers and coexisting hypertension (30)(31)(32), a meta-analysis and data pooling study showed that narrow retinal arteriolar calibers appear to precede clinical hypertension (33). Therefore, a plausible explanation for the link between narrower arteriolar caliber and incident DN seen in this population, compared with previously studied cohorts, is a higher prevalence of hypertension after the baseline examination.…”

Section: Discussionmentioning

confidence: 99%

Retinal Vessel Calibers Predict Long-term Microvascular Complications in Type 1 Diabetes: The Danish Cohort of Pediatric Diabetes 1987 (DCPD1987)

et al. 2014

View full text Add to dashboard Cite

Diabetic neuropathy, nephropathy, and retinopathy cause significant morbidity in patients with type 1 diabetes, even though improvements in treatment modalities delay the appearance and reduce the severity of these complications. To prevent or further delay the onset, it is necessary to better understand common underlying pathogenesis and to discover preclinical biomarkers of these complications. Retinal vessel calibers have been associated with the presence of microvascular complications, but their long-term predictive value has only been sparsely investigated. We examined retinal vessel calibers as 16-year predictors of diabetic nephropathy, neuropathy, and proliferative retinopathy in a young population-based Danish cohort with type 1 diabetes. We used semiautomated computer software to analyze vessel diameters on baseline retinal photos. Calibers of all vessels coursing through a zone 0.5-1 disc diameter from the disc margin were measured and summarized as the central artery and vein equivalents. In multiple regression analyses, we found wider venular diameters and smaller arteriolar diameters were both predictive of the 16-year development of nephropathy, neuropathy, and proliferative retinopathy. Early retinal vessel caliber changes are seemingly early markers of microvascular processes, precede the development of microvascular complications, and are a potential noninvasive predictive test on future risk of diabetic retinopathy, neuropathy, and nephropathy.Diabetic microvascular complications, namely diabetic peripheral neuropathy (DPN), diabetic nephropathy (DN), and diabetic retinopathy (DR), are common in type 1 diabetes (1) despite advances in metabolic care. Identifying new predictors of microvascular disease could be helpful for early individual risk stratification, which may provide better opportunity for timely implementation of effective interventions. For this purpose, the retinal vasculature provides a unique opportunity to assess vascular health directly and noninvasively in vivo.Studies have investigated how retinal vessel calibers are associated with microvascular complications in both type 1 and type 2 diabetes (2-14). The evidence to date suggests that wider retinal venular diameters are associated with presence of both DN and severe levels of DR in several cross-sectional studies (3,(8)(9)(10) and with incident DN (4,5) and progression to severe

show abstract

“…Several longitudinal studies among adults have shown that retinal arteriolar narrowing, likely indicative of increased peripheral vascular resistance, is associated with increased risks of hypertension in later life, and can therefore be used as an early marker of cardiovascular disease risk. 11,27 Also, studies among children aged 6 to 8 and 12.7 years have shown that narrower retinal arterioles were significantly correlated with increased risks of hypertension. 12 Our results suggest that reduced maternal second trimester PlGF levels, which are associated with a suboptimal placenta development and the risk of adverse pregnancy outcomes, 7,8 might also lead to narrowing of microvasculature in later life.…”

Section: Interpretation Of Main Findingsmentioning

confidence: 99%

Influence of Maternal Angiogenic Factors During Pregnancy on Microvascular Structure in School-Age Children

et al. 2015

View full text Add to dashboard Cite

Reduced placental growth factor (PlGF) levels and higher soluble fms-like tyrosine kinase (sFlt-1) levels in mothers during pregnancy may have persistent effects on vascular structures in their offspring. We examined whether angiogenic factors during pregnancy also affect childhood retinal microvasculature in a population-based prospective cohort study among 3505 mothers and their children. We measured maternal PlGF and sFlt-1 in the first and second trimester of pregnancy. At the age of 6, we measured childhood retinal arteriolar and venular calibers from digitized retinal photographs. We performed multiple linear regression models, taking maternal and childhood sociodemographic and lifestyle-related characteristics, birth characteristics, and childhood current body mass index and blood pressure into account. We observed that first trimester maternal PlGF and sFlt-1 levels were not associated with childhood retinal arteriolar caliber. Lower second trimester maternal PlGF levels, but not sFlt-1 levels, were associated with narrower childhood retinal arteriolar caliber (difference: −0.09 SD score [95% confidence interval, −0.16 to 0.01], per SD score decrease in PlGF). This association was not explained by maternal and childhood sociodemographic and lifestyle-related characteristics, birth characteristics, or childhood current body mass index and blood pressure. Maternal PlGF and sFlt-1 levels in the first or second trimester were not associated with childhood retinal venular caliber. Our results suggest that lower maternal second trimester PlGF levels affect the microvascular development in the offspring, leading to narrower retinal arteriolar caliber in childhood. Further studies are needed to confirm these findings and to explore the underlying mechanisms and long-term cardiovascular consequences.

show abstract

Retinal Microvasculature as a Model to Study the Manifestations of Hypertension

Cited by 222 publications

References 124 publications

Long Noncoding RNA-GAS5

Long Noncoding RNA-GAS5

Retinal Vessel Calibers Predict Long-term Microvascular Complications in Type 1 Diabetes: The Danish Cohort of Pediatric Diabetes 1987 (DCPD1987)

Influence of Maternal Angiogenic Factors During Pregnancy on Microvascular Structure in School-Age Children

Contact Info

Product

Resources

About