This is a very tricky one to answer since, whilst most large vessels use mainly nitric oxide, small vessels, depending on the vascular bed or exact vascular regions, use different mechanisms of endothelium-dependent dilation. Endothelial function in the microcirculation comes under the broad term endothelium-derived hyperpolarization. Some vessels use transferable hyperpolarizing factors, whereas others use gap junctions to transmit hyperpolarization from endothelium to smooth muscle. Circulating levels of epoxyeicosatrienoic acids are often used as a marker for EDH/microvascular function, but in reality this would be compared with analyses of isolated tissue to pin down the mechanism in the vessel of interest. A global marker for EDH activity isn't really a feasible approach.

Acetylcholine iontophoresis is commonly used as a test for endothelial function in the skin microvasculature. It is non-invasive and easy to perform. Perhaps this could be combined with flow-mediated dilatation of the brachial artery or venous occlusion plethysmogaphy? 

See for instance: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4354622/

Alternatively, it could study vessels in histological sections. Although it is an expensive and invasive method, you can measure with accuracy the caliber of vessels, to study individually the endothelium, the media l and the adventitia (by immunohistochemical method). You can still make three-dimensional reconstruction of these vessels, since the microscopic study alone does not always allow to evaluate the function of these vessels. A site for removal of material for study can be mesenteric region of vessels in patients treated by urgent surgery (see for example http://www.bibliotecadigital.unicamp.br/document/? code = vtls000239211).

I hope this information proves helpful

The answer is except from a review "Biomarkers of endothelial cell activation serve as potential surrogate markers for drug-induced vascular injury" *Jun Zhang et al., 2010; Toxicilogic pathology 38:856-871). 

Endothelial cell activation may also lead to endothelial dysfunction. Endothelial dysfunction can manifest as imbalance between relaxing and contrast factors, nitric oxide and endothelin; between procoagulant and anticoagulant mediators; or between growth-inhibiting and growth-promoting substance. endothelial dysfunction can be produced by uncontrolled chronic and persistent endothelial cell activation. 

E-selectin is a specific marker of endothelial activation, which is induced in vivo and reflects functional alterations of endothelial cells. Because E-selectin is expressed solely on the activate endothelial cells, presence of E-selectin in the blood is taken as conclusive evidence of endothelial activation.  

E-selectin induced by cytokine is expressed on the endothelium of venules or capillaries, but not the endothelium of arterioles or arteries. In a mouse model of endotoxin-stimulated endothelial activation, E-selectin is expressed on the endothelium of medium- or small-sized veins, but not on the endothelium of the aorta.

Therefore, E-selectin can be used to distinguish endothelial dysfunction between large blood vessel (aorta) from small blood vessels (post-capillary venules and capillaries).

In addition, another review may provide some clues to answer this question (Jun Zhang et al., Biomarkers of endothelial cell activation: candidate markers for drug-induced vasculitis in patients or drug-induced vascular injury in animals. Vascular Pharmacology 2012; 56:14-25). In patients with large vessel vasculitis, TANTES (regulated on activation, normal T cell expressed and secreted) is a specific marker; in patients with medium vessel vasculitis, SAA (serum amyloid-A) is a specific marker; and in patients with small vessel vasculitis, several markers (sIL-ra, PTX3, stPA, TNF, MCP, sTF) can be used for diagnosis.    

You could consider functional assay of vascular function, such as Flow Mediated Dilation, which has both large vessel (brachial artery dilation) aspect and a micro vessel (reactive hyperemia) aspect. Addition of such functional assessment to the above mentioned circulating markers would be an ideal combination of parallel measurements. 

I would recommend you to contact to Hetty de Boer ([email protected])

Hello. Giwa et al. performed human anatopahological studies of brains with small vessels diseases radiological features in order to determine endothelial dysfunction. Also, the LIMITS study looked for serum biomarkers in small vessels diease. In summary:

1. Endothelial thrombomodulin increased in SVD, probably as a protective

agent. (Giwa et. al)

2. Endothelial ICAM1 and IL-6 were rarely seen, and were not related to SVD. (Giwa et. al)

3. Among recent lacunar stroke patients, hsCRP levels predict the risk of recurrent strokes and other vascular

events. (LIMITS study).

4. Among recent lacunar stroke patients, IL6 and TNF receptor concentrations

predict risk of recurrent vascular events, and are associated with the effect of antiplatelet therapies. (LIMITS study).

I also attach a systematic review of endothelial dysfunction in SVD: Sorry I focus only in CSVD, but it´s the field I ´ve been doing some recent research.

I hope you found this useful. 

Bye.