The effect of aging on the cutaneous microvasculature

Bentov, Itay; Reed, May J.

doi:10.1016/j.mvr.2015.04.004

Cited by 82 publications

(51 citation statements)

References 127 publications

(118 reference statements)

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“…Lastly, the dermal concentrations of local anesthetics have not been measured; we chose a hypothetical concentration for local anesthetic exposure that was similar for both young and aged HFB. Since there is a decrease in the dermal microcirculation in aged skin (54), it is likely that reduced blood flow increases the concentration of local anesthetics by decreasing uptake and subsequent clearance. We propose that age-related deficits in the dermal circulation enhance, rather than reduce, the effect of lidocaine on aged HFB.…”

Section: Discussionmentioning

confidence: 99%

Lidocaine Impairs Proliferative and Biosynthetic Functions of Aged Human Dermal Fibroblasts

Bentov

Damodarasamy

Spiekerman³

et al. 2016

Anesthesia &Amp; Analgesia

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Background The aged are at increased risk of postoperative wound healing complications. Since local anesthetics are commonly infiltrated into the dermis of surgical wounds, we sought to determine if local anesthetics adversely affect proliferative and biosynthetic functions of dermal fibroblasts. We also evaluated the effect of local anesthetics on IGF-1 and TGF-ß1, growth factors that are important regulators of wound healing. Methods Human dermal fibroblasts from aged and young donors (HFB) were exposed to local anesthetic agents at clinically relevant concentrations. We screened the effects of lidocaine, bupivacaine, mepivacaine and ropivacaine on proliferation of HFB. Lidocaine was the most detrimental to proliferation in HFB. We then evaluated the effect of lidocaine on expression and function of the growth factors, IGF-1 and TGF-ß1. Lastly, concurrent exposure to lidocaine and IGF-1 or TGF-ß1 were evaluated for their effects on proliferation and expression of dermal collagens, respectively. Results Lidocaine and mepivacaine inhibited proliferation in aged HFB (for lidocaine 88% of control, 95%CI 80%-98%, p=0.009 and for mepivacaine 90% of control, 95%CI 81%-99%, p=0.032), but not in young HFB. Ropivicaine and bupivicaine did not inhibit proliferation. Due to the clinical utility of lidocaine relative to mepivicaine, we focused on lidocaine. Lidocaine decreased proliferation in aged HFB, which was abrogated by IGF-1. Lidocaine inhibited transcripts for IGF-1 and IGF1R in fibroblasts from aged donors (IGF-1, log2 fold-change −1.25 {42% of control, 95%CI 19%-92%, p=0.035} and IGF1R, log2 fold-change of −1.00 {50% of control, 95%CI 31%-81%, p=0.014}). In contrast, lidocaine did not effect the expression of IGF-1 or IGF1R transcripts in the young HFB. Transcripts for collagen III were decreased after lidocaine exposure in aged and young HFB (log2 fold-change −1.28 {41% of control, 95%CI 20%-83%, p=0.022} in aged HFB and log2 fold-change −1.60 {33% of control, 95%CI 15%-73%, p=0.019} in young HFB). Transcripts for collagen I were decreased in aged HFB (log2 fold-change −1.82 {28% of control 95%CI 14%-58%, p=0.006}), but were not in the young HFB. Similar to the transcripts, lidocaine also inhibited the protein expression of collagen III in young and aged HFB (log2 fold-change −1.79 {29% of control, 95%CI 18%-47%, p=0.003} in young HFB and log2 fold-change −1.76 {30% of control, 95%CI 9%-93%, p=0.043} in aged HFB). The effect of lidocaine on expression of collagen III protein was obviated by TGF-ß1 in both young and aged HFB. Conclusions Our results show that lidocaine inhibits processes relevant to dermal repair in aged HFB. The detrimental responses to lidocaine are due, in part, to interactions with IGF-1 and TGF-ß1.

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Section: Discussionmentioning

confidence: 99%

Lidocaine Impairs Proliferative and Biosynthetic Functions of Aged Human Dermal Fibroblasts

Bentov

Damodarasamy

Spiekerman³

et al. 2016

Anesthesia &Amp; Analgesia

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“…Since Rho kinase activation has been shown to be regulated by ROS in vascular smooth muscle cells [86], it seems reasonable to propose that age-induced microvascular constriction is also regulated by Nox-mediated ROS signaling. Furthermore, aging is associated with arteriolar stiffness, decreased vascular density and impaired microvascular organization [5]. Nevertheless, signaling mechanisms that underlie the co-existence of Nox-mediated oxidative stress, aging and microvascular pathologies warrant further investigation.…”

Section: Systemic Microcirculationmentioning

confidence: 99%

“…This is also achieved by an ensemble of responses elicited by endothelial cells and smooth muscle cells [1,2]. Impaired arteriolar function, as observed in various cardiovascular pathologies such as hypertension, diabetes, stroke and aging, leads to vascular remodeling, tissue ischemia and organ damage [3,5–8]. Emerging evidence has shown that changes in the oxidative environment are often accompanied by the aforementioned vascular dysfunction and cardiovascular diseases in the microcirculation [6,9–12].…”

Section: Introductionmentioning

confidence: 99%

Microvascular NADPH oxidase in health and disease

Pagano

2017

Free Radical Biology and Medicine

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The systemic and cerebral microcirculation contribute critically to regulation of local and global blood flow and perfusion pressure. Microvascular dysfunction, commonly seen in numerous cardiovascular pathologies, is associated with alterations in the oxidative environment including potentiated production of reactive oxygen species (ROS) and subsequent activation of redox signaling pathways. NADPH oxidases (Noxs) are a primary source of ROS in the vascular system and play a central role in cardiovascular health and disease. In this review, we focus on the roles of Noxs in ROS generation in resistance arterioles and capillaries, and summarize their contributions to microvascular physiology and pathophysiology in both systemic and cerebral microcirculation. In light of the accumulating evidence that Noxs are pivotal players in vascular dysfunction of resistance arterioles, selectively targeting Nox isozymes could emerge as a novel and effective therapeutic strategy for preventing and treating microvascular diseases.

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“…It is known that there are age‐related anatomical and functional changes in the microcirculation, such as increased stiffness, decreased density, impaired organization, and decreased reactivity. The dental pulp also demonstrates age‐related changes similar to other parts of the body .…”

Section: Introductionmentioning

confidence: 99%