Microangiopathy

Microangiopathies are involved in a variety of different diseases including:

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 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]

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 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]