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. Author manuscript; available in PMC: 2011 Mar 11.
Published in final edited form as: Physiol Rev. 1995 Jul;75(3):519–560. doi: 10.1152/physrev.1995.75.3.519

TABLE 1.

Shear stress and related mechanical stress responses in endothelial cells (arranged in order of response time)

Effect Force Cell Type and
Response Time		 Significance Reference
Number
K+ channel activation,
    hyperpolarization (Whole cell
    recording)		 LSS; 0.2–16.5 dyn/cm2 BAEC; s Related to vasorelaxation 51, 163, 271
Rb+ efflux stimulated LSS, 1–10 dyn/cm2 PAEC Graded transient increase of K+
    permeability		 6
Hyperpolarization (Vm-sensitive dyes) LSS; 10–120 dyn/cm2 BPAEC; steady state
    at 60 s		 As above 250
Activation of nonselective cation
    channels (membrane patch)		 Suction (pressure, stretch);
    10–20 mmHg		 PAEC; ms Endothelial stretch-activated
    channels		 190
Intracellular Ca2+ rise (fluo 3) Mechanical poking and
    dimpling		 HUVEC; s Stretch-activated Ca2+ channels;
    depolarization.		 115
Large increase in release of NO LSS; 8 dyn/cm2 BAEC; s Flow-mediated vasorelaxation 51, 96, 258, 262,
    364, 375, 376
Release of ATP, acetylcholine,
    endothelin, and substance P		 Flow through microcarrier bed HUVEC; s Neurotransmitter release 26, 27, 237, 294
Stimulation of PA and PE hydrolysis LSS; 1.4 and 22 dyn/cm2 HUVEC; 10–30 s Additional sources of AA;
    implies activation of PLA2 		22
Decrease of intracellular pH LSS; 0.5–13.4 dyn/cm2 BAEC Modulation of ionic balance 406
Transient elevation of IP3; biphasic
    (BAEC)		 LSS; 30 and 60 dyn/cm2; cyclic
    stretch		 BAEC, HUVEC; >15–
    30 s; major peak at
    5 min (BAEC)		 Phosphoinositides as second
    messenger for shear stress
    transduction		 20, 22, 260
Intracellular Ca2+ rise; Ca2+
    oscillations		 LSS; 0.2–4.0 dyn/cm2 BAEC; 15–40 s Ca2+ as second messenger 7, 106, 332, 339
Flow modulation of effects of
    vasoactive agonists ATP and
    bradykinin		 LSS; 0–30 dyn/cm2 BAEC; s Indirect stimulation via agonist
    receptor mechanisms		 82, 83, 239, 261,
    341
cGMP increased 3-fold via a NO-
    dependent mechanism; endothelial
    K+ channel implicated		 LSS; 0–40 dyn/cm2 BAEC; 60 s Vasoregulation mechanisms 264
Transient elevation of IP3 Cyclic strain; 24% deformation;
    1 Hz		 HSVEC Phosphoinositides as second
    messengers for strain
    deformation		 293, 310
Sustained PGI2 release; G proteins
    implicated		 LSS; 0–9 and 14.0 dyn/cm2 HUVEC; 2 min PGI2 regulation of vascular tone 19, 95
Pulsed PGI2 release at higher level
    than steady flow		 LSS (pulsatile); mean 10 dyn/
    cm2 		HUVEC; <1 min Antithrombotic properties 118
Augmented factor Xa production
    (indicative of enhanced tissue
    factor activity)		 LSS; 0.7 and 2.7 dyn/cm2 Activated HUVEC;
    min		 Enhanced procoagulant activity 119
Vascular free radical generation Perfusion rates 2–12 ml/min Ex vivo artery; 10
    min		 Unknown 191
Stimulation of mitogen-activated
    protein kinases (MAPK); 35 dyn/
    cm2 peak		 LSS; 3.5–117 dyn/cm2 BAEC; 5 min, peak
    20–30 min		 Involvement of membrane
    mitogen receptor-like
    pathway in shear
    transduction		 B. Berk, personal
    communication
Activation of NFκB LSS; 10 dyn/cm2 BAEC; 20 min Transcription factor activation 186, 301
Induction of c-myc, jun LSS; 10 dyn/cm2 BAEC; 30 min Immediate early growth
    response genes		 146, 186
Activation of adenylyl cyclase Cyclic stretching; osmotic
    swelling		 BAEC, HUVEC; min cAMP as second messenger for
    stretch		 192, 385
Directional remodeling of focal
    adhesion sites; Realignment with
    flow (>8 h)		 LSS; 10 dyn/cm2 BAEC; min, h Cell attachment site
    involvement in transmission
    and/or transduction of stress		 68, 304
Tension controls cell shape, pH, and
    growth via extracellular matrix-
    integrin binding		 Modulation of inherent cell
    tension		 Capillary EC; <1 h Integrins regulate cell growth
    via cell tension		 156
Downregulation of VCAM-1
    expression		 LSS; 0–7.2 dyn/cm2 Mouse lymph node
    endothelial cells;
    >1 h		 Preferential leukocyte adhesion
    at low shear stress		 266, 321
10-Fold enhancement of PDGF-A
    mRNA; PDGF-A peak at 1.5–2 h		 LSS; 0–51 dyn/cm2 HUVEC, BAEC; >1 h Enhanced mitogen secretion;
    regulation of SMC growth		 147, 216, 238
2- to 3-fold increase of PDGF-B
    mRNA followed by 4-fold decrease
    by 9 h; PKC dependence
    controversial		 LSS; 10–36 dyn/cm2 steady,
    pulsatile, turbulent		 HUVEC, BAEC; 1–9 h Identification of shear stress
    response element of PDGF-B
    gene		 147, 238, 301
bFGF mRNA stimulated 1.5- to 5-fold LSS; 15 and 36 dyn/cm2 BAEC; 0.5–9 h, peak
    at 6 h		 Peptide growth factor
    regulation		 216
Pinocytosis stimulated; adaptation by
    6 h		 LSS; >5 dyn/cm2 BAEC; <2 h Plasma membrane vesicle
    formation rate transiently
    elevated		 61
Induction of c-fos; 50% block by PKC
    inhibitor		 LSS; 4–25 dyn/cm2 BAEC; 1–2 h Early growth response gene 146, 148, 295
Increased TGF-β1 mRNA and
    biologically active TGF protein		 LSS; 20 dyn/cm2 BAEC; 2 h Inhibition of smooth muscle
    growth		 265
Upregulation of ICAM-1 mRNA and
    protein and enhanced lymphocyte
    adhesion; downregulated by 6 h		 LSS; 2.5–46 dyn/cm2 HUVEC; 2 h Enhanced binding of LFA-1-
    positive cells		 249, 321
Stimulation of IL-6 secretion and
    gene expression		 LSS; >10 dyn/cm2 HUVEC; 2 h Cytokine secretion 223
Redistribution of Golgi apparatus
    and MTOC to upstream location in
    cell; normalized by 24 h		 LSS; 22 and 88 dyn/cm2 BCAEC; >2 h Temporary displacement of
    organelles		 47
Induction of protein kinase C LSS; >10 dyn/cm2 BAEC; <3 h Regulation of protein
    phosphorylation		 181
Endothelin mRNA and protein
    secretion reported to be both
    stimulated and downregulated;
    mechanism appears to involve
    filamentous actin and microtubules		 LSS; 5–20 dyn/cm2 PAEC and BAEC;
    peak at 2–6 h		 Regulation of vasoconstriction 214, 215, 243,
    338, 398
NO synthase mRNA and protein
    stimulated		 LSS; 15 dyn/cm2; flow through
    microcarrier bed; 0.5–2.0
    ml/min		 BAEC; 3 h Vasorelaxation 182, 258, 285,
    375, 376
HSP 70 mRNA increased 2- to 4-fold LSS; bidirectional BAEC; 4 h HSP 70 shock response to flow 139
tPA mRNA expression and secretion
    stimulated		 LSS; 15 and 25 dyn/cm2 HUVEC; 5 h Enhancement of fibrinolytic
    activity		 79–81
Cell proliferation in quiescent
    monolayer		 Turbulent flow; average shear
    stress 1.5–15.0 dyn/cm2 		BAEC; >3 h Loss of contact inhibition of
    growth by disturbed flow		 63
Cell alignment in direction of flow;
    function of time and magnitude of
    shear stress		 LSS; >5 dyn/cm2 All types; >6 h Minimizes drag on cell 78, 85, 187, 193,
    194
F-actin cytoskeletal and fibronectin
    rearrangement		 LSS; >5 dyn/cm2 and in vivo All types; >6 h Associated with cell
    realignment		 78, 97, 169, 189,
    274, 388, 389
Differential cell shape and alignment
    responses; corresponding F-actin
    changes		 LSS; pulsatile 1 Hz; sinusoidal
    flows of various patterns up
    to 60 dyn/cm2 		BAEC; >6 h Discrimination between
    different types of pulsatile
    flows		 133, 134, 254, 255
Cell realignment perpendicular to
    strain; protein synthesis increased;
    F-actin redistribution
    perpendicular to strain		 Cyclic biaxial deformation;
    0.78–12%; 1-Hz frequency
    20–24% strain; 0.9–1.0 Hz		 BPAEC; >7 h
    HUVEC, HSVEC; 15
    min		 Stretching of artery by blood
    pulsation; separation of strain
    and shear stress effects		 152, 343, 358
Histamine release and histamine
    decarboxylase activity stimulated		 Oscillatory LSS; range, 1.6–8.2
    dyn/cm2 		BAEC; >6 h Modulation of endothelial
    permeability barrier		 348
Decreased thrombomodulin mRNA
    and protein at 15 and 36 dyn/cm2 		LSS; 4, 15, and 36 dyn/cm2 BAEC; 9 h Protective role against
    thrombosis in regions of low
    shear stress		 217
Increased thrombomodulin activity
    (synthesis of activated protein C)		 LSS; 25 dyn/cm2 HUVEC; 24 h Protective in regions of higher
    shear stress		 321
Downregulation of fibronectin
    synthesis		 LSS; 24 dyn/cm2 + 20 mmHg
    hydrostatic pressure		 HUVEC; 12 and 48 h Altered cell adhesion; platelet-
    endothelial interactions		 124
Regional cell cycle stimulation in
    confluent monolayer		 Disturbed laminar flow (flow
    separation, vortex,
    reattachment); 0–10 dyn/cm2 		BAEC; 12 h Steep shear gradients stimulate
    cell turnover; focal
    hemodynamic effects		 76
Reorganized topography of luminal
    surface at subcellular resolution		 LSS; 12 dyn/cm2 BAEC; 24 h Reduced gradients of shear
    stress in aligned cells; force
    transmission altered		 15, 16, 395
Mechanical stiffness of cell surface
    proportional to extent of
    realignment to flow		 LSS; 10–85 dyn/cm2 BAEC; 24 h Decreased deformability of
    subplasma membrane cortical
    complex		 323
LDL metabolism stimulated LSS; 30 and 60 dyn/cm2 BAEC; 24 h Endothelial cholesterol balance 351
Increase in class I and induction of
    class II MHC antigen expression		 LSS; 3–36 dyn/cm2 Fat, omentum, and
    brain microvessels;
    24–36 h		 Role of flow in immune
    response		 221
Inhibition of endothelial cell division LSS BAEC; 24–48 h Regulation of endothelial
    regeneration		 407
Inhibition of collagen synthesis and
    stimulation of cell growth		 Cyclic biaxial stretch; 3 cycles/
    min; 24% deformation		 BAEC, myocytes; 5
    days		 Inverse relationship related to
    endothelial repair
    mechanisms		 359

LSS, laminar shear stress; BAEC, bovine aortic endothelial cells; Vm, membrane potential; BPAEC, bovine pulmonary artery endothelial cells; PAEC, porcine aortic endothelial cells; BCAEC, bovine carotid artery endothelial cells; IP3, inositol trisphosphate; HUVEC, human umbilical vein endothelial cells; HAEC, human aortic endothelial cells; PGI2, prostaglandin I2 (prostacyclin); tPA, tissue plasminogen activator; NO, nitric oxide; AA, arachidonic acid; PLA2, phospholipase A2; PDGF-A, PDGF-B, platelet-derived growth factor A and B chains, respectively; SMC, vascular smooth muscle cells; HSVEC, human saphenous vein endothelial cells; MTOC, microtubule organizing center; LDL, low-density lipoproteins; MHC, major histocompatibility complex; HSP 70, 70-kDa heat-shock protein.