Circulating humanin levels are associated with preserved coronary endothelial function

Widmer, R. Jay; Flammer, Andreas J.; Herrmann, Joerg; Rodriguez-Porcel, Martin; Wan, Junxiang; Cohen, Pinchas; Lerman, Lilach O.; Lerman, Amir

doi:10.1152/ajpheart.00765.2012

Cited by 104 publications

(92 citation statements)

References 31 publications

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“…Similar percentages of the 47 ED subjects and 33 control subjects were smokers, had hypertension and/or diabetes, and were on statin and/or aspirin therapy. As previously reported, levels of inflammatory markers (hs-CRP, P= 0.95) and traditional lipid CVD risk factors—including HDL-C ( P= 0.052), LDL-C ( P= 0.64), triglycerides ( P= 0.14), and Lp(a) ( P= 0.62)—did not differ significantly between the control and ED groups 35–38 .…”

Section: Resultssupporting

confidence: 68%

Patients With Coronary Endothelial Dysfunction Have Impaired Cholesterol Efflux Capacity and Reduced HDL Particle Concentration

Monette

Hutchins

Ronsein

et al. 2016

Circulation Research

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Rationale Coronary endothelial dysfunction (ED)–an early marker of atherosclerosis–increases the risk of cardiovascular events. Objective We tested the hypothesis that cholesterol efflux capacity and HDL particle concentration predict coronary ED better than HDL-cholesterol (HDL-C). Methods and Results We studied 80 subjects with non-obstructive (<30% stenosis) coronary artery disease. ED was defined as <50% change in coronary blood flow in response to intra-coronary infusions of acetylcholine during diagnostic coronary angiography. Cholesterol efflux capacity and HDL particle concentration (HDL-PIMA) were assessed with validated assays. Cholesterol efflux capacity and HDL-PIMA were both strong, inverse predictors of ED (P<0.001 and 0.005, respectively). In contrast, HDL-C and other traditional lipid risk factors did not differ significantly between control and ED subjects. Large HDL particles were markedly decreased in ED subjects (33%; P=0.005). After correction for HDL-C, both efflux capacity and HDL-PIMA remained significant predictors of ED status. HDL-PIMA explained cholesterol efflux capacity more effectively than HDL-C (r=0.54 and 0.36, respectively). The efflux capacities of isolated HDL and serum HDL correlated strongly (r=0.49). Conclusions Cholesterol efflux capacity and HDL-PIMA are reduced in subjects with coronary ED, independently of HDL-C. Alterations in HDL-PIMA and HDL itself account for a much larger fraction of the variation in cholesterol efflux capacity than does HDL-C. A selective decrease in large HDL particles may contribute to impaired cholesterol efflux capacity in ED subjects. These observations support a role for HDL size, concentration and function as markers—and perhaps mediators—of coronary atherosclerosis in humans.

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Section: Resultssupporting

confidence: 68%

Patients With Coronary Endothelial Dysfunction Have Impaired Cholesterol Efflux Capacity and Reduced HDL Particle Concentration

Monette

Hutchins

Ronsein

et al. 2016

Circulation Research

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“…HN is expressed in the endothelial cell layer of human arteries and veins [7] and in carotid atherosclerotic plaques [8]. HN has also been detected in human skeletal muscle [9], plasma [10], testis and sperm [11]. HNr was shown to be expressed in a number of adult rat tissues such as cerebral cortex, hippocampus, heart, testis and uterus, among others [12].…”

Section: Introductionmentioning

confidence: 99%

Antiapoptotic Factor Humanin Is Expressed in Normal and Tumoral Pituitary Cells and Protects Them from TNF-α-Induced Apoptosis

et al. 2014

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Humanin (HN) is a 24-amino acid peptide with cytoprotective action in several cell types such as neurons and testicular germ cells. Rattin (HNr), a homologous peptide of HN expressed in several adult rat tissues, also has antiapoptotic action. In the present work, we demonstrated by immunocytochemical analysis and flow cytometry the expression of HNr in the anterior pituitary of female and male adult rats as well as in pituitary tumor GH3 cells. HNr was localized in lactotropes and somatotropes. The expression of HNr was lower in females than in males, and was inhibited by estrogens in pituitary cells from both ovariectomized female and orquidectomized male rats. However, the expression of HNr in pituitary tumor cells was not regulated by estrogens. We also evaluated HN action on the proapoptotic effect of TNF-α in anterior pituitary cells assessed by the TUNEL method. HN (5 µM) per se did not modify basal apoptosis of anterior pituitary cells but completely blocked the proapoptotic effect of TNF-α in total anterior pituitary cells, lactotropes and somatotropes from both female and male rats. Also, HN inhibited the apoptotic effect of TNF-α on pituitary tumor cells. In summary, our results demonstrate that HNr is present in the anterior pituitary gland, its expression showing sexual dimorphism, which suggests that gonadal steroids may be involved in the regulation of HNr expression in this gland. Antiapoptotic action of HN in anterior pituitary cells suggests that this peptide could be involved in the homeostasis of this gland. HNr is present and functional in GH3 cells, but it lacks regulation by estrogens, suggesting that HN could participate in the pathogenesis of pituitary tumors.

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“…The study protocol has been described in detail elsewhere (12,16,20,21). In brief, patients presenting to the catheterization laboratory with nonobstructive CAD (<40% stenosis) underwent invasive coronary microvascular functional testing using an intracoronary Doppler guidewire.…”

Section: Methodsmentioning

confidence: 99%

“…Impaired endothelial-independent microvascular function was defined as a coronary flow velocity reserve ratio in response to adenosine of #2.5 (22). Impaired endothelial-dependent microvascular function was defined as a maximal percentage increase in CBF in response to any dose of acetylcholine compared with baseline of #50% (16,17,21). A decrease in coronary artery diameter of $20% in response to acetylcholine compared with baseline was in keeping with epicardial endothelial dysfunction (16,17,21 Figure 1 There was a wide distribution of measurements of coronary flow velocity reserve (CFR) in response to adenosine and coronary blood flow (CBF) in response to acetylcholine among all patients presenting with chest pain and nonobstructive coronary artery disease.…”

Section: Methodsmentioning

confidence: 99%

“…Impaired endothelial-dependent microvascular function was defined as a maximal percentage increase in CBF in response to any dose of acetylcholine compared with baseline of #50% (16,17,21). A decrease in coronary artery diameter of $20% in response to acetylcholine compared with baseline was in keeping with epicardial endothelial dysfunction (16,17,21 Figure 1 There was a wide distribution of measurements of coronary flow velocity reserve (CFR) in response to adenosine and coronary blood flow (CBF) in response to acetylcholine among all patients presenting with chest pain and nonobstructive coronary artery disease. I indicates normal CBF response to acetylcholine and normal CFR response to adenosine; II indicates abnormal CBF response to acetylcholine and normal CFR response to adenosine; III indicates normal CBF response to acetylcholine and abnormal CFR response to adenosine; and IV indicates abnormal CBF response to acetylcholine and abnormal CFR response to adenosine.…”

Section: Methodsmentioning

confidence: 99%

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Prevalence of Coronary Microvascular Dysfunction Among Patients With Chest Pain and Nonobstructive Coronary Artery Disease

Sara

Widmer

Matsuzawa

et al. 2015

JACC: Cardiovascular Interventions

413

315

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Circulating humanin levels are associated with preserved coronary endothelial function

Cited by 104 publications

References 31 publications

Patients With Coronary Endothelial Dysfunction Have Impaired Cholesterol Efflux Capacity and Reduced HDL Particle Concentration

Patients With Coronary Endothelial Dysfunction Have Impaired Cholesterol Efflux Capacity and Reduced HDL Particle Concentration

Antiapoptotic Factor Humanin Is Expressed in Normal and Tumoral Pituitary Cells and Protects Them from TNF-α-Induced Apoptosis

Prevalence of Coronary Microvascular Dysfunction Among Patients With Chest Pain and Nonobstructive Coronary Artery Disease

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