Structural Microangiopathies in Skeletal Muscle Related to Systemic Vascular Pathologies in Humans

Baum, Oliver; Bernd, Jonathan; Becker, Samuel S.; Odriozola, Adolfo; Zuber, Benoît; Tschanz, Stefan A.; Zakrzewicz, Andreas; Egginton, Stuart; Berkholz, Janine

doi:10.3389/fphys.2020.00028

Cited by 14 publications

(12 citation statements)

References 40 publications

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“…Furthermore, the effects of the MMP family specifically on patients with type 2 diabetes mellitus (T2DM) and advancement of cardiovascular, organ, and tissue damage were shown to correlate with a high level of MMP-12 in T2DM patients [155]. The observation of increased MMP activity in T2DM patients was also made in other studies [156]. As an example, uncontrolled glycemic conditions in T2DM patients were particularly identified with modifications in periodontal tissues; therefore, the severity in periodontitis is analogous to a measurement of T2DM disease progression [157].…”

Section: Mps In Cardiovascular Diseasesmentioning

confidence: 63%

Metalloproteinases and Their Inhibitors: Potential for the Development of New Therapeutics

Raeeszadeh‐Sarmazdeh

Linh

Hritz

2020

Cells

216

155

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The metalloproteinase (MP) family of zinc-dependent proteases, including matrix metalloproteinases (MMPs), a disintegrin and metalloproteases (ADAMs), and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) plays a crucial role in the extracellular matrix (ECM) remodeling and degradation activities. A wide range of substrates of the MP family includes ECM components, chemokines, cell receptors, and growth factors. Metalloproteinases activities are tightly regulated by proteolytic activation and inhibition via their natural inhibitors, tissue inhibitors of metalloproteinases (TIMPs), and the imbalance of the activation and inhibition is responsible in progression or inhibition of several diseases, e.g., cancer, neurological disorders, and cardiovascular diseases. We provide an overview of the structure, function, and the multifaceted role of MMPs, ADAMs, and TIMPs in several diseases via their cellular functions such as proteolysis of other cell signaling factors, degradation and remodeling of the ECM, and other essential protease-independent interactions in the ECM. The significance of MP inhibitors targeting specific MMP or ADAMs with high selectivity is also discussed. Recent advances and techniques used in developing novel MP inhibitors and MP responsive drug delivery tools are also reviewed.

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Section: Mps In Cardiovascular Diseasesmentioning

confidence: 63%

Metalloproteinases and Their Inhibitors: Potential for the Development of New Therapeutics

Raeeszadeh‐Sarmazdeh

Linh

Hritz

2020

Cells

216

155

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“…Indeed, the peri-capillary basement membrane was 38.5 and 45.5% thicker ( p < 0.05) in people suffering from diabetes mellitus type 2 or intermittent claudication—peripheral arterial disease—than in healthy patients and people with arterial hypertension. The proportion of capillaries with disrupted BM between pericytes and EC was higher ( p < 0.05) in arterial hypertension patients (33.2%) and people with diabetes mellitus type 2 (38.7%) than in the control patients [ 180 ]. Breaks in the TJ bands (crests) lead to brain oedema [ 80 ].…”

Section: Discussionmentioning

confidence: 99%

“…ECs of the pulmonary trunk have many caveolae [ 175 ]. Multicaveolar endothelium has been observed in arteries, blood capillaries of the heart (see also Figures 16–36 presented by Rhodin [ 108 ]); striated muscles, dermal blood capillaries [ 176 , 177 ] (see also Figure 2A presented by Braverman [ 178 ], the uterus (see Figures 16–38a presented by Rhodin [ 108 ], Figure 2A presented by Racho El-Akouri et al [ 179 ], and Figure 1 presented by Baum et al [ 180 ]), adipose tissue (see also Figures 2 and 15 presented by Blanchette-Machie and Scow [ 181 ]; Figure 1 presented by Ghinea et al [ 182 ]; Figures 3 and 5 presented by Cinti [ 183 ]). Caveolae are observed in the ECs of lung arteries and capillaries as well as well as in ECs of peritubular blood capillaries in the kidney (see Figures 16–37 presented by Rhodin [ 108 ]).…”

Section: Classification Of Ecsmentioning

confidence: 99%

Intracellular Membrane Transport in Vascular Endothelial Cells

Mirоnоv

Mironov

Sanavio

et al. 2023

IJMS

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The main component of blood and lymphatic vessels is the endothelium covering their luminal surface. It plays a significant role in many cardiovascular diseases. Tremendous progress has been made in deciphering of molecular mechanisms involved into intracellular transport. However, molecular machines are mostly characterized in vitro. It is important to adapt this knowledge to the situation existing in tissues and organs. Moreover, contradictions have accumulated within the field related to the function of endothelial cells (ECs) and their trans-endothelial pathways. This has induced necessity for the re-evaluation of several mechanisms related to the function of vascular ECs and intracellular transport and transcytosis there. Here, we analyze available data related to intracellular transport within ECs and re-examine several hypotheses about the role of different mechanisms in transcytosis across ECs. We propose a new classification of vascular endothelium and hypotheses related to the functional role of caveolae and mechanisms of lipid transport through ECs.

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“…In total, the extra drop in the interstitial fluid due to the glucose removed by the microdialysis probe is equal to: Equation (10) can thus be rewritten in terms of known parameters as: Baum et al, 2020;Bigler et al, 2016;Gidlöf et al, 1988) S probe Microdialysis probe exchange surface 2 r 1 L m 2 (Müller et al, 1996) V i Relative interstitial volume in the tissue 20% No unit (Aukland and Nicolaysen, 1981;Barison et al, 2015;Mingrone et al, 2001;Yamada et al, 2017)…”

Section: Modeling Glucose Removal By a Microdialysis Probementioning

confidence: 99%

Modeling the measurement bias in interstitial glucose concentrations derived from microdialysis in skeletal muscle

Angleys

Østergaard

2022

Physiological Reports

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Muscle tissue utilizes glucose as a fuel during exercise and stores glucose in form of glycogen during rest. The associated glucose transport includes delivery of glucose from blood plasma into the interstitial space and subsequent, GLUT‐4 facilitated diffusion into muscle cells. The extent to which the vascular endothelium acts as a barrier to glucose transport, however, remains debated. While accurate measurements of interstitial glucose concentration (IGC) are key to resolve this debate, these are also challenging as removal of interstitial fluid may perturb glucose transport and therefore bias IGC measurements. We developed a three‐compartment model to infer IGC in skeletal muscle from its local metabolism and blood flow. The model predicts that IGC remains within 5% of that of blood plasma during resting conditions but decreases more as metabolism increases. Next, we determined how microdialysis protocols affect IGC. Our model analysis suggests that microdialysis‐based IGC measurements underestimate true values. Notably, reported increases in muscle capillary permeability surface area product (PS) to glucose under the condition of elevated metabolism may owe in part to such measurements bias. Our study demonstrates that microdialysis may be associated with significant measurement bias in the context of muscle IGC assessment. Reappraising literature data with this bias in mind, we find that muscle capillary endothelium may represent less of a barrier to glucose transport in muscle than previously believed. We discuss the impact of glucose removal on the microdialysis relative recovery and means of correcting microdialysis IGC values.

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Structural Microangiopathies in Skeletal Muscle Related to Systemic Vascular Pathologies in Humans

Cited by 14 publications

References 40 publications

Metalloproteinases and Their Inhibitors: Potential for the Development of New Therapeutics

Metalloproteinases and Their Inhibitors: Potential for the Development of New Therapeutics

Intracellular Membrane Transport in Vascular Endothelial Cells

Modeling the measurement bias in interstitial glucose concentrations derived from microdialysis in skeletal muscle

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