Changes in red blood cell membrane structure in pulmonary arterial hypertension

2016 ◽  
Author(s):  
Alice Huertas ◽  
Ly Tu ◽  
Raphael Thuillet ◽  
Carole Phan ◽  
Jennifer Bordenave ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Cell Membrane ◽  
Blood Cell ◽  
Arterial Hypertension ◽  
Red Blood Cell ◽  
Membrane Structure ◽  
Red Blood Cell Membrane ◽  
Pulmonary Arterial

scholarly journals A Markedly Disrupted Skeletal Network With Abnormally Distributed Intramembrane Particles in Complete Protein 4.1-Deficient Red Blood Cells (Allele 4.1 Madrid): Implications Regarding a Critical Role of Protein 4.1 in Maintenance of the Integrity of the Red Blood Cell Membrane

Blood ◽  
1997 ◽  
Vol 90 (6) ◽  
pp. 2471-2481 ◽  
Author(s):  
Ayumi Yawata ◽  
Akio Kanzaki ◽  
Florinda Gilsanz ◽  
Jean Delaunay ◽  
Yoshihito Yawata
Keyword(s):  
Cell Membrane ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Membrane Structure ◽  
Critical Role ◽  
Electron Microscopic ◽  
Intramembrane Particles ◽  
Protein 4.1 ◽  
Red Blood Cell Membrane

Abstract Electron microscopic (EM) studies were performed to clarify the interactions of membrane proteins in the red blood cell membrane structure in situ of a homozygous patient with total deficiency of protein 4.1 who carried a point mutation of the downstream translation initiation codon (AUG → AGG) of the protein 4.1 gene [the 4.1 (−) Madrid; Dalla Venezia et al, J Clin Invest 90:1713, 1992]. Immunologically, as expected, protein 4.1 was completely missing in the red blood cell membrane structure in situ. A markedly disrupted skeletal network was observed by EM using the quick-freeze deep-etching method and the surface replica method, although the number of spectrin molecules was only minimally reduced (395 ± 63/μm2; normal, 504 ± 36/μm2). The number of basic units in the skeletal network was strikingly reduced (131 ± 21/μm2; normal, 548 ± 39/μm2), with decreased small-sized units (17 ± 4/μm2; normal, 384 ± 52/μm2) and increased large-sized units (64% ± 14%; normal, 5% ± 1%). Concomitantly, immuno-EM disclosed striking clustering of spectrin molecules with aggregated ankyrin molecules in the red blood cell membrane structure in situ. Although no quantitative abnormalities in the number and size distribution of the intramembrane particles were observed, there was a disappearance of regular distribution, with many clusters of various sizes, probably reflecting the distorted skeletal network. Therefore, protein 4.1 suggests by EM to play a crucial role in maintenance of the normal integrity of the membrane structure in situ not only of the skeletal network but also of the integral proteins.

scholarly journals A Markedly Disrupted Skeletal Network With Abnormally Distributed Intramembrane Particles in Complete Protein 4.1-Deficient Red Blood Cells (Allele 4.1 Madrid): Implications Regarding a Critical Role of Protein 4.1 in Maintenance of the Integrity of the Red Blood Cell Membrane

Blood ◽  
1997 ◽  
Vol 90 (6) ◽  
pp. 2471-2481
Author(s):  
Ayumi Yawata ◽  
Akio Kanzaki ◽  
Florinda Gilsanz ◽  
Jean Delaunay ◽  
Yoshihito Yawata
Keyword(s):  
Cell Membrane ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Membrane Structure ◽  
Critical Role ◽  
Electron Microscopic ◽  
Intramembrane Particles ◽  
Protein 4.1 ◽  
Red Blood Cell Membrane

Electron microscopic (EM) studies were performed to clarify the interactions of membrane proteins in the red blood cell membrane structure in situ of a homozygous patient with total deficiency of protein 4.1 who carried a point mutation of the downstream translation initiation codon (AUG → AGG) of the protein 4.1 gene [the 4.1 (−) Madrid; Dalla Venezia et al, J Clin Invest 90:1713, 1992]. Immunologically, as expected, protein 4.1 was completely missing in the red blood cell membrane structure in situ. A markedly disrupted skeletal network was observed by EM using the quick-freeze deep-etching method and the surface replica method, although the number of spectrin molecules was only minimally reduced (395 ± 63/μm2; normal, 504 ± 36/μm2). The number of basic units in the skeletal network was strikingly reduced (131 ± 21/μm2; normal, 548 ± 39/μm2), with decreased small-sized units (17 ± 4/μm2; normal, 384 ± 52/μm2) and increased large-sized units (64% ± 14%; normal, 5% ± 1%). Concomitantly, immuno-EM disclosed striking clustering of spectrin molecules with aggregated ankyrin molecules in the red blood cell membrane structure in situ. Although no quantitative abnormalities in the number and size distribution of the intramembrane particles were observed, there was a disappearance of regular distribution, with many clusters of various sizes, probably reflecting the distorted skeletal network. Therefore, protein 4.1 suggests by EM to play a crucial role in maintenance of the normal integrity of the membrane structure in situ not only of the skeletal network but also of the integral proteins.

scholarly journals Hemin_Induced Changes in the Red Blood Cell Membrane Structure

2012 ◽  
Vol 8 (6) ◽  
pp. 5
Author(s):  
V. V. Moroz ◽  
E. K. Kozlova ◽  
A. M. Chernysh ◽  
O. E. Gudkova ◽  
A. V. Bushuyeva
Keyword(s):  
Cell Membrane ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Membrane Structure ◽  
Red Blood Cell Membrane

scholarly journals Biventricular diastolic dysfunction, thrombocytopenia, and red blood cell macrocytosis in experimental pulmonary arterial hypertension

2020 ◽  
Vol 10 (2) ◽  
pp. 204589402090878
Author(s):  
Ji Young Lee ◽  
Karen A. Fagan ◽  
Chun Zhou ◽  
Lynn Batten ◽  
Michael V. Cohen ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Blood Cell ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Diastolic Dysfunction ◽  
Red Blood Cell ◽  
Tissue Doppler ◽  
Tissue Hypoperfusion ◽  
Pulmonary Arterial

Pulmonary arterial hypertension is a fatal disease, where death is associated with right heart failure and reduced cardiorespiratory reserve. The Sugen 5416, hypoxia and normoxia Fischer rat model mimics human pulmonary arterial hypertension, although the cause(s) of death remains incompletely understood. Here, we hypothesized that these animals develop biventricular diastolic dysfunction that contributes to tissue hypoperfusion coincident with severe pulmonary arterial hypertension. We performed comprehensive echocardiographic and hematologic assessments. Serial echocardiogram at 3–5 weeks was performed followed by blood sampling via aortic or cardiac puncture. Echocardiogram revealed pulmonary arterial hypertension in pulmonary artery Doppler waves, including notched wave envelopes, and decreased pulmonary artery acceleration time/pulmonary artery ejection time ratio and right ventricular outflow tract velocity time integral. Impaired right ventricular systolic function, assessed by decreased tricuspid annular plane systolic excursion and tricuspid tissue Doppler systolic positive wave velocity, was observed in pulmonary arterial hypertension. Tricuspid and mitral pulsed wave and tissue Doppler findings suggested biventricular diastolic dysfunction, with dynamic changes in early and late diastolic filling waves, their fusion patterns, and a decrease in e' velocity. Heart rate and ejection fraction did not change, but cardiac output, stroke volume, and end-diastolic volume were decreased, and inferior vena cava respiratory variation was decreased. Blood electrolyte values were suggestive of intravascular volume expansion early in the disease followed by volume contraction and tissue hypoperfusion in the latter stages of disease. Complete blood count showed thrombocytopenia and non-anemic macrocytosis with reticulocytosis and an increase in red blood cell distribution width. Thus, pulmonary, cardiac, and hematological findings in Fischer animals with pulmonary arterial hypertension are characteristic of humans and provide an insightful experimental platform to resolve mechanisms of disease progression.

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