Pericyte constriction underlies capillary derecruitment during hyperemia in the setting of arterial stenosis

Carmen Methner, Anusha Mishra, Kirsti Golgotiu, Yuandong Li, Wei Wei, Norbert Yanez, Berislav Zlokovic, Ruikang K. Wang, Nabil Alkayed, Sanjiv Kaul, Jeffrey Iliff

Research output: Contribution to journalArticle

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Abstract

Capillary derecruitment distal to a coronary stenosis is implicated as the mechanism of reversible perfusion defect and potential myocardial ischemia during coronary hyperemia; however, the underlying mechanisms are not defined. We tested whether pericyte constriction underlies capillary derecruitment during hyperemia under conditions of stenosis. In vivo two-photon microscopy (2PM) and optical microangiography (OMAG) were used to measure hyperemia-induced changes in capillary diameter and perfusion in wild-type and pericyte-depleted mice with femoral artery stenosis. OMAG demonstrated that hyperemic challenge under stenosis produced capillary derecruitment associated with decreased RBC flux. 2PM demonstrated that hyperemia under control conditions induces 26 + 5% of capillaries to dilate and 19 + 3% to constrict. After stenosis, the proportion of capillaries dilating to hyperemia decreased to 14 + 4% (P ± 0.05), whereas proportion of constricting capillaries increased to 32 + 4% (P ± 0.05). Hyperemia-induced changes in capillary diameter occurred preferentially in capillary segments invested with pericytes. In a transgenic mouse model featuring partial pericyte depletion, only 14 + 3% of capillaries constricted to hyperemic challenge after stenosis, a significant reduction from 33 + 4% in wild-type littermate controls (P ± 0.04). These results provide for the first time direct visualization of hyperemia-induced capillary derecruitment distal to arterial stenosis and demonstrate that pericyte constriction underlies this phenomenon in vivo. These results could have important therapeutic implications in the treatment of exercise-induced ischemia. NEW & NOTEWORTHY In the setting of coronary arterial stenosis, hyperemia produces a reversible perfusion defect resulting from capillary derecruitment that is believed to underlie cardiac ischemia under hyperemic conditions. We use optical microangiography and in vivo two-photon microscopy to visualize capillary derecruitment distal to a femoral arterial stenosis with cellular resolution. We demonstrate that capillary constriction in response to hyperemia in the setting of stenosis is dependent on pericytes, contractile mural cells investing the microcirculation.

Original languageEnglish (US)
Pages (from-to)H255-H263
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume317
Issue number2
DOIs
StatePublished - Aug 1 2019

Fingerprint

Pericytes
Hyperemia
Constriction
Pathologic Constriction
Perfusion
Coronary Stenosis
Photons
Microscopy
Ischemia
Femoral Artery
Microcirculation
Thigh
Transgenic Mice
Myocardial Ischemia

Keywords

  • Capillaries
  • Derecruitment
  • Ischemia
  • Pericytes
  • Stenosis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Pericyte constriction underlies capillary derecruitment during hyperemia in the setting of arterial stenosis. / Methner, Carmen; Mishra, Anusha; Golgotiu, Kirsti; Li, Yuandong; Wei, Wei; Yanez, Norbert; Zlokovic, Berislav; Wang, Ruikang K.; Alkayed, Nabil; Kaul, Sanjiv; Iliff, Jeffrey.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 317, No. 2, 01.08.2019, p. H255-H263.

Research output: Contribution to journalArticle

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abstract = "Capillary derecruitment distal to a coronary stenosis is implicated as the mechanism of reversible perfusion defect and potential myocardial ischemia during coronary hyperemia; however, the underlying mechanisms are not defined. We tested whether pericyte constriction underlies capillary derecruitment during hyperemia under conditions of stenosis. In vivo two-photon microscopy (2PM) and optical microangiography (OMAG) were used to measure hyperemia-induced changes in capillary diameter and perfusion in wild-type and pericyte-depleted mice with femoral artery stenosis. OMAG demonstrated that hyperemic challenge under stenosis produced capillary derecruitment associated with decreased RBC flux. 2PM demonstrated that hyperemia under control conditions induces 26 + 5{\%} of capillaries to dilate and 19 + 3{\%} to constrict. After stenosis, the proportion of capillaries dilating to hyperemia decreased to 14 + 4{\%} (P ± 0.05), whereas proportion of constricting capillaries increased to 32 + 4{\%} (P ± 0.05). Hyperemia-induced changes in capillary diameter occurred preferentially in capillary segments invested with pericytes. In a transgenic mouse model featuring partial pericyte depletion, only 14 + 3{\%} of capillaries constricted to hyperemic challenge after stenosis, a significant reduction from 33 + 4{\%} in wild-type littermate controls (P ± 0.04). These results provide for the first time direct visualization of hyperemia-induced capillary derecruitment distal to arterial stenosis and demonstrate that pericyte constriction underlies this phenomenon in vivo. These results could have important therapeutic implications in the treatment of exercise-induced ischemia. NEW & NOTEWORTHY In the setting of coronary arterial stenosis, hyperemia produces a reversible perfusion defect resulting from capillary derecruitment that is believed to underlie cardiac ischemia under hyperemic conditions. We use optical microangiography and in vivo two-photon microscopy to visualize capillary derecruitment distal to a femoral arterial stenosis with cellular resolution. We demonstrate that capillary constriction in response to hyperemia in the setting of stenosis is dependent on pericytes, contractile mural cells investing the microcirculation.",
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AU - Mishra, Anusha

AU - Golgotiu, Kirsti

AU - Li, Yuandong

AU - Wei, Wei

AU - Yanez, Norbert

AU - Zlokovic, Berislav

AU - Wang, Ruikang K.

AU - Alkayed, Nabil

AU - Kaul, Sanjiv

AU - Iliff, Jeffrey

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AB - Capillary derecruitment distal to a coronary stenosis is implicated as the mechanism of reversible perfusion defect and potential myocardial ischemia during coronary hyperemia; however, the underlying mechanisms are not defined. We tested whether pericyte constriction underlies capillary derecruitment during hyperemia under conditions of stenosis. In vivo two-photon microscopy (2PM) and optical microangiography (OMAG) were used to measure hyperemia-induced changes in capillary diameter and perfusion in wild-type and pericyte-depleted mice with femoral artery stenosis. OMAG demonstrated that hyperemic challenge under stenosis produced capillary derecruitment associated with decreased RBC flux. 2PM demonstrated that hyperemia under control conditions induces 26 + 5% of capillaries to dilate and 19 + 3% to constrict. After stenosis, the proportion of capillaries dilating to hyperemia decreased to 14 + 4% (P ± 0.05), whereas proportion of constricting capillaries increased to 32 + 4% (P ± 0.05). Hyperemia-induced changes in capillary diameter occurred preferentially in capillary segments invested with pericytes. In a transgenic mouse model featuring partial pericyte depletion, only 14 + 3% of capillaries constricted to hyperemic challenge after stenosis, a significant reduction from 33 + 4% in wild-type littermate controls (P ± 0.04). These results provide for the first time direct visualization of hyperemia-induced capillary derecruitment distal to arterial stenosis and demonstrate that pericyte constriction underlies this phenomenon in vivo. These results could have important therapeutic implications in the treatment of exercise-induced ischemia. NEW & NOTEWORTHY In the setting of coronary arterial stenosis, hyperemia produces a reversible perfusion defect resulting from capillary derecruitment that is believed to underlie cardiac ischemia under hyperemic conditions. We use optical microangiography and in vivo two-photon microscopy to visualize capillary derecruitment distal to a femoral arterial stenosis with cellular resolution. We demonstrate that capillary constriction in response to hyperemia in the setting of stenosis is dependent on pericytes, contractile mural cells investing the microcirculation.

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