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Microangiopathy

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(Redirected from Small vessel disease)

Microangiopathy (also known as microvascular disease, small vessel disease (SVD) or microvascular dysfunction) is a disease of the microvessels, small blood vessels in the microcirculation.[1] It can be contrasted to macroangiopathies such as atherosclerosis, where large and medium-sized arteries (e.g., aorta, carotid and coronary arteries) are primarily affected.[2]

Microangiopathy
A case of conjunctival microangiopathy (red dashed-square) secondary to diabetes demonstrating a microaneurysm (orange arrow), vessel dilatation (blue arrows), and vascular tortuosity (yellow arrow).
Examples of microvascular diseases.

Small vessel diseases (SVDs) affect primarily organs that receive significant portions of cardiac output such as the brain, the kidney, and the retina. Thus, SVDs are a major etiologic cause in debilitating conditions such as renal failure, blindness, lacunar infarcts, and dementia.[3]

Types

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Microangiopathies are involved in a variety of different diseases including:

Pathophysiology

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The main target of small vessel diseases is the endothelium, which plays a key role in vascular homeostasis.[3] The pathogenesis of SVDs in various organs is characterized by endothelial dysfunction, capillary rarefaction, microthrombi and microvascular remodeling.[15]

Diabetic microangiopathy, which is the most common cause of microangiopathy, is more prevalent in the kidney, retina and vascular endothelium since glucose transport in these sites isn’t regulated by insulin and these tissues cannot stop glucose from entering cells when blood sugar levels are high.[16] Among all biochemical mechanisms involved in diabetic vascular damage such as the polyol pathway and the renin–angiotensin system (RAS), the advanced glycation end products (AGEs) pathway appears to be the most important in the pathogenesis and progression of microvascular complications.[17]

Chronic high blood sugar levels lead to the attachment of sugar molecules to various proteins, including collagen, laminin, and peripheral nerve proteins. This process, called glycosylation, creates advanced glycation end products (AGEs). AGEs formation cross-links these proteins, making them resistant to degradation. This leads to accumulation of AGEs, thickening of the basement membrane, narrowing the blood vessels, reducing blood flow to the tissues and causing ischemic injury.[18][19]

In addition, oxidative stress, caused by AGEs and the other pathways, causes apoptosis of pericytes and podocytes in the retina and the kidneys respectively leading to capillary wall fragility and increased vascular leakage. This results in local swelling (e.g. macular edema) and impaired tissue function.[20]

Microvascular diseases as a multisystem disorder

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Some researchers have suggested that SVD may be a multisystem disorder, meaning that it can affect multiple organs in the body, including the heart and brain. This is supported by multiple studies stating that cardiac pathologies are more prevalent in patients with pathological evidence of cerebrovascular SVD and vice versa.[15][21]

Coronary microvascular diseases (CMDs) can be caused by:[5]

On the other hand, Cerebral SVD encompasses a range of vascular pathologies including arteriosclerosis-related CSVD, where lipohyalinosis causes stenosis of the lumen of the arterioles and amyloid-related CSVD, characterized by the build-up of β-amyloid deposits in small- and medium-caliber cerebral vessels.[6]

The vascular anatomy of the heart and brain is similar in that conduit arteries are distributed on the surface of these organs with tissue perfusion achieved through deep penetrating arteries. Both coronary and cerebral microvascular diseases do share some common risk factors such as hypertension. Why some patients with microvascular angina subsequently develop vascular cognitive impairment and others do not is an unanswered question. Potential underpinning mechanisms include premature vascular aging and clustering of vascular risk factors leading to an accelerated cardiovascular risk.[21]

Diagnosis

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The diagnosis of microangiopathies can be based on direct visualization of the microcirculation, imaging modalities (e.g. MRI), conventional testings (e.g. ophthalmoscopy for diabetic retinopathy) or other diagnostic measures (e.g. blood smear for schistocytes in thrombotic microangiopathies).[6][8][16]

For assessment of the morphological and functional aspects of microcirculation, nailfold videocapillaroscopy (NVC) can be used, in which videocapillaroscopy is performed at the nailfold, where capillaries are arranged with the longitudinal axis parallel to the skin surface, so that they can be examined along their entire length.[8]

NVC has been largely used not only for investigating peripheral microangiopathy, but also as a sort of "window" to systemic microvascular dysfunction. Although its main application is within the connective tissue diseases such as systemic scleroderma and dermatomyositis, it has been employed in non-rheumatic diseases with microvascular involvement such as diabetes mellitus, essential hypertension and COVID-19 infection.[8]

Nailfold capillaroscopy
Capillaroscopic findings in patients with mild COVID-19
  1. Enlarged loops (Black arrow)
  2. Microhemorrhages (Red arrow)
  3. Microthrombosis (Green arrow)

Optical coherence tomography angiography (OCTA) is another imaging modality that offers high-resolution visualization of the retinal capillary network and can be used to evaluate microcirculation in conditions such as diabetic retinopathy.[22] Many studies have demonstrated that evaluation of the retinal microvascular changes using OCTA or other methods such as fluorescein angiography may reflect the systemic microvascular functions as in patients with coronary microvascular disease, cerebral small vessel diseases or systemic sclerosis (The potential of retinal microvascularopathy as a biomarker for assessing microvascular status of other circulations).[23][24]

Unlike the retinal microcirculation, the coronary microvasculature cannot be directly imaged. Instead, a number of different tests can be used to measure how much blood is flowing through the coronary microvasculature. These tests can be used to assess how well the coronary microvasculature is functioning and to diagnose coronary microvascular disease.[5] They include non-invasive measures such as cardiac MRI and invasive measures such as intracoronary Doppler wire.[25]

Similarly, CSVD is typically recognized on both brain magnetic resonance imaging (MRI) and computed tomography (CT) scans, but MRI has greater sensitivity and specificity. Neuroimaging of CSVD primarily involves visualizing radiological phenotypes of CSVD such as recent subcortical infarcts or cerebral microbleeds (CMBs).[6]

Treatment

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Treatment options of microangiopathies can be directed at:

A better understanding of the mechanisms leading to damage of small blood vessels may be associated with novel therapeutic approaches, the safety and efficacy of some of which will need to be further investigated. Examples include calcium dobesilate and aldose reductase inhibitors in diabetic microangiopathies and endothelin receptor antagonists for pulmonary hypertension.[16][21][27][28]

References

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  1. ^ "microangiopathy" at Dorland's Medical Dictionary
  2. ^ Kumar, Vinay; Abbas, Abul K.; Aster, Jon C.; Perkins, James A.; Robbins, Stanley L.; Cotran, Ramzi S. (2015). Robbins and Cotran pathologic basis of disease (Ninth ed.). Philadelphia, Pa: Elsevier; Saunders. ISBN 978-1-4557-2613-4.
  3. ^ a b Hakim, Antoine M. (24 September 2019). "Small Vessel Disease". Frontiers in Neurology. 10: 1020. doi:10.3389/fneur.2019.01020. ISSN 1664-2295. PMC 6768982. PMID 31616367. This article incorporates text available under the CC BY 4.0 license.
  4. ^ Sugimoto, Kazuhiro; Murakami, Hiroshi; Deguchi, Takahisa; Arimura, Aiko; Daimon, Makoto; Suzuki, Susumu; Shimbo, Takuro; Yagihashi, Soroku (2019). "Cutaneous microangiopathy in patients with type 2 diabetes: Impaired vascular endothelial growth factor expression and its correlation with neuropathy, retinopathy and nephropathy". Journal of Diabetes Investigation. 10 (5): 1318–1331. doi:10.1111/jdi.13020. ISSN 2040-1116. PMC 6717820. PMID 30719863.
  5. ^ a b c Camici, Paolo G.; Crea, Filippo (22 February 2007). "Coronary microvascular dysfunction". The New England Journal of Medicine. 356 (8): 830–840. doi:10.1056/NEJMra061889. ISSN 1533-4406. PMID 17314342.
  6. ^ a b c d Litak, Jakub; Mazurek, Marek; Kulesza, Bartłomiej; Szmygin, Paweł; Litak, Joanna; Kamieniak, Piotr; Grochowski, Cezary (20 December 2020). "Cerebral Small Vessel Disease". International Journal of Molecular Sciences. 21 (24): 9729. doi:10.3390/ijms21249729. ISSN 1422-0067. PMC 7766314. PMID 33419271. This article incorporates text available under the CC BY 4.0 license.
  7. ^ Pereira Fontes, Carla; Fonseca, Samuel (2021). "Pseudothrombotic Microangiopathy as a Rare Presentation of Cobalamin Deficiency". Cureus. 13 (8): e17184. doi:10.7759/cureus.17184. ISSN 2168-8184. PMC 8439408. PMID 34540418.
  8. ^ a b c d Gualtierotti, Roberta; Fox, Sharon E.; Da Silva Lameira, Fernanda; Giachi, Andrea; Valenti, Luca; Borghi, Maria Orietta; Meroni, Pier Luigi; Cugno, Massimo; Peyvandi, Flora (28 May 2023). "Nailfold Videocapillaroscopic Alterations as Markers of Microangiopathy in COVID-19 Patients". Journal of Clinical Medicine. 12 (11): 3727. doi:10.3390/jcm12113727. ISSN 2077-0383. PMC 10253962. PMID 37297922. This article incorporates text available under the CC BY 4.0 license.
  9. ^ Prommer, Hans-Ulrich; Maurer, Johannes; von Websky, Karoline; Freise, Christian; Sommer, Kerstin; Nasser, Hamoud; Samapati, Rudi; Reglin, Bettina; Guimarães, Pedro; Pries, Axel Radlach; Querfeld, Uwe (28 March 2018). "Chronic kidney disease induces a systemic microangiopathy, tissue hypoxia and dysfunctional angiogenesis". Scientific Reports. 8 (1): 5317. Bibcode:2018NatSR...8.5317P. doi:10.1038/s41598-018-23663-1. ISSN 2045-2322. PMC 5871820. PMID 29593228.
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  11. ^ Lambova, Sevdalina Nikolova (10 February 2023). "Microangiopathy in Rheumatic Diseases". Life. 13 (2): 491. doi:10.3390/life13020491. ISSN 2075-1729. PMC 9965541. PMID 36836847.
  12. ^ Martinelli, Anthony W.; Dunn, William; McClure, Mark E.; Walker, Ieuan; Stewart, Andrew; Karia, Sumit; Preston, Stephen D.; Thiru, Sathia; Torpey, Nicholas; Ojha, Sanjay; Symington, Emily; Nathan, James A. (November 2022). "A Case of Thrombotic Microangiopathy and Acute Sarcoidosis". Chest. 162 (5): e245–e248. doi:10.1016/j.chest.2022.06.023. ISSN 0012-3692. PMC 9752182. PMID 36344132.
  13. ^ Koike, Haruki; Katsuno, Masahisa (5 February 2019). "Ultrastructure in Transthyretin Amyloidosis: From Pathophysiology to Therapeutic Insights". Biomedicines. 7 (1): 11. doi:10.3390/biomedicines7010011. ISSN 2227-9059. PMC 6466231. PMID 30764529.
  14. ^ Cesarone, M. R.; Belcaro, G.; Geroulakos, G.; Griffin, M.; Ricci, A.; Brandolini, R.; Pellegrini, L.; Dugall, M.; Ippolito, E.; Candiani, C.; Simeone, E.; Errichi, B. M.; Di Renzo, A. (April 2003). "Flight microangiopathy on long-haul flights: prevention of edema and microcirculation alterations with Venoruton". Clinical and Applied Thrombosis/Hemostasis. 9 (2): 109–114. doi:10.1177/107602960300900203. ISSN 1076-0296. PMID 12812378. S2CID 1605773.
  15. ^ a b Feuer, Daniel S.; Handberg, Eileen M.; Mehrad, Borna; Wei, Janet; Merz, C. Noel Bairey; Pepine, Carl J.; Keeley, Ellen C. (2022). "Microvascular dysfunction as a systemic disease: A review of the evidence". The American Journal of Medicine. 135 (9): 1059–1068. doi:10.1016/j.amjmed.2022.04.006. ISSN 0002-9343. PMC 9427712. PMID 35472396.
  16. ^ a b c d e f g Khalil, H. (November 2017). "Diabetes microvascular complications-A clinical update". Diabetes & Metabolic Syndrome. 11 (Suppl 1): S133–S139. doi:10.1016/j.dsx.2016.12.022. ISSN 1878-0334. PMID 27993541.
  17. ^ Mengstie, Misganaw Asmamaw; Chekol Abebe, Endeshaw; Behaile Teklemariam, Awgichew; Tilahun Mulu, Anemut; Agidew, Melaku Mekonnen; Teshome Azezew, Muluken; Zewde, Edgeit Abebe; Agegnehu Teshome, Assefa (15 September 2022). "Endogenous advanced glycation end products in the pathogenesis of chronic diabetic complications". Frontiers in Molecular Biosciences. 9: 1002710. doi:10.3389/fmolb.2022.1002710. ISSN 2296-889X. PMC 9521189. PMID 36188225.
  18. ^ Cecil, Russell La Fayette; Goldman, Lee; Schafer, Andrew I. (2012). Goldman's Cecil medicine (24th ed.). Philadelphia: Elsevier/Saunders. ISBN 978-1-4377-1604-7.
  19. ^ Somboonwong, Juraiporn; Yusuksawad, Mariem; Keelawat, Somboon; Thongruay, Sirima; Poumsuk, Ubon (2016). "Minimization of the Risk of Diabetic Microangiopathy in Rats by Nigella sativa". Pharmacognosy Magazine. 12 (Suppl 2): S175–S180. doi:10.4103/0973-1296.182169. ISSN 0973-1296. PMC 4883076. PMID 27279704.
  20. ^ Madonna, Rosalinda; Balistreri, Carmela Rita; Geng, Yong-Jian; De Caterina, Raffaele (March 2017). "Diabetic microangiopathy: Pathogenetic insights and novel therapeutic approaches". Vascular Pharmacology. 90: 1–7. doi:10.1016/j.vph.2017.01.004. ISSN 1879-3649. PMID 28137665.
  21. ^ a b c Berry, Colin; Sidik, Novalia; Pereira, Anthony C.; Ford, Thomas J.; Touyz, Rhian M.; Kaski, Juan-Carlos; Hainsworth, Atticus H. (2 February 2019). "Small-Vessel Disease in the Heart and Brain: Current Knowledge, Unmet Therapeutic Need, and Future Directions". Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease. 8 (3): e011104. doi:10.1161/JAHA.118.011104. ISSN 2047-9980. PMC 6405580. PMID 30712442. This article incorporates text available under the CC BY 4.0 license.
  22. ^ Le, Patrick H.; Patel, Bhupendra C. (2023). "Optical Coherence Tomography Angiography". StatPearls. StatPearls Publishing. PMID 33085382. Retrieved 29 September 2023.
  23. ^ Sideri, Anna-Maria; Kanakis, Menelaos; Katsimpris, Andreas; Karamaounas, Aristotelis; Brouzas, Dimitrios; Petrou, Petros; Papakonstaninou, Evangelia; Droutsas, Konstantinos; Kandarakis, Stylianos; Giannopoulos, Georgios; Georgalas, Ilias (5 May 2023). "Correlation Between Coronary and Retinal Microangiopathy in Patients With STEMI". Translational Vision Science & Technology. 12 (5): 8. doi:10.1167/tvst.12.5.8. ISSN 2164-2591. PMC 10168007. PMID 37145590.
  24. ^ Tang, Qian; Zhang, Yanli; Yang, Zhengfang; Li, Siou; Wu, Meini; Guo, Yongming; Zhao, Weina; Yin, Changhao (9 June 2022). "Study on the Interaction between the Characteristics of Retinal Microangiopathy and Risk Factors for Cerebral Small Vessel Disease". Contrast Media & Molecular Imaging. 2022: 9505945. doi:10.1155/2022/9505945. ISSN 1555-4309. PMC 9203197. PMID 35800241.
  25. ^ a b c d Taqueti, Viviany R.; Di Carli, Marcelo F. (27 November 2018). "Coronary Microvascular Disease Pathogenic Mechanisms and Therapeutic Options: JACC State-of-the-Art Review". Journal of the American College of Cardiology. 72 (21): 2625–2641. doi:10.1016/j.jacc.2018.09.042. ISSN 0735-1097. PMC 6296779. PMID 30466521.
  26. ^ a b c Chojdak-Łukasiewicz, Justyna; Dziadkowiak, Edyta; Zimny, Anna; Paradowski, Bogusław (March 2021). "Cerebral small vessel disease: A review". Advances in Clinical and Experimental Medicine. 30 (3): 349–356. doi:10.17219/acem/131216. ISSN 1899-5276. PMID 33768739. S2CID 232365709.
  27. ^ Zhang, XinYuan; Liu, Wei; Wu, ShanShan; Jin, JingLong; Li, WeiHong; Wang, NingLi (2014-12-20). "Calcium dobesilate for diabetic retinopathy: a systematic review and meta-analysis". Science China Life Sciences. 58 (1): 101–107. doi:10.1007/s11427-014-4792-1. ISSN 1674-7305. PMID 25528255.
  28. ^ Haller, Hermann; Ji, Linong; Stahl, Klaus; Bertram, Anna; Menne, Jan (2017). "Molecular Mechanisms and Treatment Strategies in Diabetic Nephropathy: New Avenues for Calcium Dobesilate—Free Radical Scavenger and Growth Factor Inhibition". BioMed Research International. 2017: 1909258. doi:10.1155/2017/1909258. ISSN 2314-6133. PMC 5634607. PMID 29082239.
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