scholarly journals APOPTOSIS CELLS OF CORONARY ARTERY WALL AS DEVELOPING AND PROGRESSING FACTOR OF CORONARY SCLEROSIS

2013 ◽  
Vol 68 (9) ◽  
pp. 22-26
Author(s):  
T. E. Vladimirskaya ◽  
I. A. Shved ◽  
S. G. Krivorot
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Coronary Artery ◽  
Smooth Muscle Cells ◽  
Coronary Arteries ◽  
Muscle Cells ◽  
Artery Wall ◽  
Paraffin Sections ◽  
Early Stages ◽  
Coronary Artery Wall

Objective: to study apoptosis of individual cellular components of the vascular wall of coronary arteries at different morphological stages of atherosclerosis. Material and methods. The study was performed on coronary arteries taken from 52 deceased patients with atherosclerosis and coronary heart disease at different stages of atherogenesis. For morphological study prepared paraffin sections, which were stained for morphological studies were prepared paraffin sections, which were stained with hematoxylin and eosin, by Van Gieson, Masson, on lipids with Sudan black B, according to Van Cossu. .To determine apoptosis, TUNEL method used in paraffin sections. Apoptotic index (AI) was calculated by TUNEL-positive cells and the average inner shell coronary artery around the perimeter each with increasing microscopic 1000. Results. Investigation showed significant apoptosis (p 0.05) increase in AI smooth muscle, endothelial cells, macrophages in the coronary arteries affected by atherosclerosis compared to intact control group vascular segments significant reduction AI endothelial, smooth muscle cells and macrophages (p  0,05) traced from the early stages of atherogenic disorders to atheromatosis. Conclusions. It is established that apoptosis of smooth muscle cells, macrophages and endothelial cells is the most intensive on early stages of atherosclerotic process. In process of progressing of atherosclerosis intensity and prevalence of apoptosis of coronary artery wall cells decreases, and processes of necrosis becomes predominant. Apoptosis of coronary artery wall cells is valuable in increasing the zones of atheromatosis, plaque destabilizations, and also increases the risk of thrombosis and ulcerations. 

14,15-Dihydroxyeicosatrienoic acid relaxes bovine coronary arteries by activation of KCa channels

2002 ◽  
Vol 282 (5) ◽  
pp. H1656-H1664 ◽  
Author(s):  
William B. Campbell ◽  
Christine Deeter ◽  
Kathryn M. Gauthier ◽  
Richard H. Ingraham ◽  
J. R. Falck ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Coronary Arteries ◽  
Epoxide Hydrolase ◽  
Muscle Cells ◽  
Kca Channels ◽  
Vasodilator Activity ◽  
Inside Out ◽  
Isolated Smooth Muscle Cells

Epoxyeicosatrienoic acids (EETs) cause vascular relaxation by activating smooth muscle large conductance Ca2+-activated K+ (KCa) channels. EETs are metabolized to dihydroxyeicosatrienoic acids (DHETs) by epoxide hydrolase. We examined the contribution of 14,15-DHET to 14,15-EET-induced relaxations and characterized its mechanism of action. 14,15-DHET relaxed U-46619-precontracted bovine coronary artery rings but was approximately fivefold less potent than 14,15-EET. The relaxations were inhibited by charybdotoxin, iberiotoxin, and increasing extracellular K+ to 20 mM. In isolated smooth muscle cells, 14,15-DHET increased an iberiotoxin-sensitive, outward K+ current and increased KCa channel activity in cell-attached patches and inside-out patches only when GTP was present. 14,15-[14C]EET methyl ester (Me) was converted to 14,15-[14C]DHET-Me, 14,15-[14C]DHET, and 14,15-[14C]EET by coronary arterial rings and endothelial cells but not by smooth muscle cells. The metabolism to 14,15-DHET was inhibited by the epoxide hydrolase inhibitors 4-phenylchalcone oxide (4-PCO) and BIRD-0826. Neither inhibitor altered relaxations to acetylcholine, whereas relaxations to 14,15-EET-Me were increased slightly by BIRD-0826 but not by 4-PCO. 14,15-DHET relaxes coronary arteries through activation of KCa channels. Endothelial cells, but not smooth muscle cells, convert EETs to DHETs, and this conversion results in a loss of vasodilator activity.

Peroxide resistance of ER Ca2+ pump in endothelium: implications to coronary artery function

1997 ◽  
Vol 273 (4) ◽  
pp. C1250-C1258 ◽  
Author(s):  
Ashok K. Grover ◽  
Sue E. Samson
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Coronary Artery ◽  
Smooth Muscle Cells ◽  
Cultured Cells ◽  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Muscle Cells ◽  
Intact Cells ◽  
Serca Pump

We examined the effects of peroxide on the sarco(endo)plasmic reticulum Ca2+ (SERCA) pump in pig coronary artery endothelium and smooth muscle at three organizational levels: Ca2+ transport in permeabilized cells, cytosolic Ca2+ concentration in intact cells, and contractile function of artery rings. We monitored the ATP-dependent, azide-insensitive, oxalate-stimulated45Ca2+uptake by saponin-permeabilized cultured cells. Low concentrations of peroxide inhibited the uptake less effectively in endothelium than in smooth muscle whether we added the peroxide directly to the Ca2+ uptake solution or treated intact cells with peroxide and washed them before the permeabilization. An acylphosphate formation assay confirmed the greater resistance of the SERCA pump in endothelial cells than in smooth muscle cells. Pretreating smooth muscle cells with 300 μM peroxide inhibited (by 77 ± 2%) the cyclopiazonic acid (CPA)-induced increase in cytosolic Ca2+ concentration in a Ca2+-free solution, but it did not affect the endothelial cells. Peroxide pretreatment inhibited the CPA-induced contraction in deendothelialized arteries with a 50% inhibitory concentration of 97 ± 13 μM, but up to 500 μM peroxide did not affect the endothelium-dependent, CPA-induced relaxation. Similarly, 500 μM peroxide inhibited the angiotensin-induced contractions in deendothelialized arteries by 93 ± 2%, but it inhibited the bradykinin-induced, endothelium-dependent relaxation by only 40 ± 13%. The greater resistance of the endothelium to reactive oxygen may be important during ischemia-reperfusion or in the postinfection immune response.

Abstract 524: Extracellular Guanosine Regulates Extracellular Adenosine Levels

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Edwin K Jackson ◽  
Delbert G Gillespie
Keyword(s):  
Blood Pressure ◽  
Endothelial Cells ◽  
Smooth Muscle ◽  
Coronary Artery ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Extracellular Adenosine ◽  
Arterial Blood

Extracellular adenosine modulates cardiovascular and renal function. While measuring extracellular purines in biological samples, we observed a correlation between levels of adenosine and guanosine. This observation led us to test the hypothesis that extracellular guanosine regulates extracellular adenosine levels in the cardiovascular and renal systems. Rat preglomerular vascular smooth muscle cells in culture were incubated with adenosine and/or guanosine. In the absence of added adenosine, exogenous guanosine (30 μmol/L) had little effect on extracellular adenosine levels, indicating that extracellular guanosine does not trigger the release or production of adenosine. Without added guanosine and 1 hour after adding 3 μmol/L of exogenous adenosine, extracellular adenosine levels were only 0.125 ± 0.020 μmol/L, indicating rapid disposition of extracellular adenosine by a monolayer of cells. In contrast, extracellular adenosine levels 1 hour after adding 3 μmol/L of adenosine plus guanosine (30 μmol/L) were 1.173 ± 0.061 μmol/L (9-fold higher; p<0.0001), indicating slow disposition of extracellular adenosine in the presence of extracellular guanosine. Extracellular guanosine impeded the disposition of extracellular adenosine not only in preglomerular vascular smooth muscle cells, but also in rat preglomerular vascular endothelial cells, mesangial cells, cardiac fibroblasts and kidney epithelial cells, as well as in human aortic vascular smooth muscle cells, coronary artery vascular smooth muscle cells and coronary artery endothelial cells. In rats, infusions of guanosine per se had little effect on cardiovascular/renal variables, yet markedly enhanced the effects of co-infusions of adenosine. For example, in control rats, adenosine (0.3 μmol/kg/min) only modestly decreased mean arterial blood pressure (from 114 ± 4 to 100 ± 4 mm Hg). In contrast, in guanosine-treated rats (10 μmol/kg/min), adenosine profoundly decreased blood pressure (from 109 ± 4 to 79 ± 3 mm Hg; p<0.0001 vs non-guanosine treated group). Conclusion: Extracellular guanosine powerfully regulates extracellular adenosine levels by altering adenosine disposition and this occurs in many, perhaps most, cell types in the cardiovascular system and kidneys.

Abstract 180: The Myristolated Alanine-Rich C Kinase Substrate (MARCKS) Differentially Regulates Proliferation of Vascular Smooth Muscle Cells and Endothelial Cells through Affecting Protein Stability and Proteolytic Processing of the Kinase Interacting with Stathmin (KIS)

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Dan Yu ◽  
Charles Drucker ◽  
Rajabrata Sarkar ◽  
Dudley K Strickland ◽  
Thomas S Monahan
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Coronary Artery ◽  
Smooth Muscle Cells ◽  
Protein Stability ◽  
Muscle Cells ◽  
Cell Types ◽  
Proteolytic Processing ◽  
Functional Domain ◽  
Human Coronary Artery

Objective: Presently, the antiproliferative agents used in drug eluting stents and drug coated balloons inhibit both VSMC and endothelial cell (EC) proliferation, and thus these patients require dual antiplatelet therapy indefinitely. Identification of a VSMC-specific target to prevent proliferation represents a significant unmet clinical need. Previously we found that knockdown of MARCKS arrests VSMC proliferation through a p27 kip1 -dependent mechanism. Interestingly MARCKS knockdown increases EC proliferation. p27 kip1 is phosphorylated by KIS allowing it to exit the nucleus and be degraded. Here we seek to understand how MARCKS influences KIS protein expression in these two cell types. Approach and Results: We performed siRNA-mediated knock down of MARCKS in human coronary artery endothelial cells (CAECs) and human coronary artery smooth muscle cells (CASMCs). MARCKS knockdown did not affect KIS mRNA expression as determined with RT-PCR in either cell type. KIS protein stability was evaluated in the presence of cyclohexamide with Western blot. In CAECs, MARCKS knockdown increased KIS stability, however, in CASMCs, MARCKS knockdown significantly decreased KIS protein stability. In CASMCs, MARCKS knockdown significantly increased KIS ubiquitinization where as in CAECs, MARCKS knockdown decreased KIS ubiquitinization. Interestingly, the well-studied functional domain of MARCKS(ED domain) is not directly involved in KIS regulation. MARCKS mutants (S4G and S4D) rescued proliferation in VSMCs. MARCKS knockdown in vivo in the murine femoral wire injury model resulted in decreased medial bromodeoxyuridine (BrdU) integration and neointima formation. MARCKS knockdown enhanced endothelial barrier function recovery four days after injury as assessed by Evans Blue integration. Conclusions: MARCKS differentially regulates the protein stability and proteolytic processing of KIS in VSMCs and ECs. The differential interaction of MARCKS and KIS likely explains the observed difference in proliferation observed with MARCKS knockdown in these two cell types.

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