Elastin Organization in Pig and Cardiovascular Disease Patients' Pericardial Resistance Arteries

Abstract

Peripheral vascular resistance is increased in essential hypertension. This involves structural changes of resistance arteries and stiffening of the arterial wall, including remodeling of the extracellular matrix. We hypothesized that biopsies of the human parietal pericardium, obtained during coronary artery bypass grafting or cardiac valve replacement surgeries, can serve as a source of resistance arteries for structural research in cardiovascular disease patients. We applied two-photon excitation fluorescence microscopy to study the parietal pericardium and isolated pericardial resistance arteries with a focus on the collagen and elastin components of the extracellular matrix. Initial findings in pig tissue were confirmed in patient biopsies. The microarchitecture of the internal elastic lamina in both the pig and patient pericardial resistance arteries (studied at a transmural pressure of 100 mm Hg) is fiber like, and no prominent external elastic lamina could be observed. This microarchitecture is very different from that in rat mesenteric arteries frequently used for resistance artery research. In conclusion, we add three-dimensional information on the structure of the extracellular matrix in resistance arteries from cardiovascular disease patients and propose further use of patient pericardial resistance arteries for studies of the human microvasculature.

Microstructure and mechanics of human resistance arteries

“…The structure of the small arteries employed in these studies using nonlinear microscopy was consistent with that observed in fixed human pericardial resistance arteries (6), with the exception that in this study no fibrous collagen was observed in the media. The structure of the two fibrous networks in the adventitia was similar to that seen in both large (10, 50) and small (6) arteries. It was notable that none of the vessels contained the fenestrated sheets of elastin reported in the intima of resistance arteries in other studies (11).…”

“…In the IEL the fibers were predominantly axially aligned at low pressure but at higher pressure spread apart to reveal gaps bridged by regularly spaced bracing fibers, which appear on the orientation plot as an emerging peak around 0°. This honeycomb-like structure has been visualized at much higher pressures (6) and its mechanical properties analyzed in large arteries (10). …”

“…Only against this background can the functional significance of changes that occur with age (12), lifestyle (18), disease (34), and body location (11) be fully understood. These objectives can be realized using nonlinear microscopy (NLM), a technique that recently has been reviewed in the context of vascular disease (32) and employed in the characterization of static resistance arteries (6). …”

Relaxing Responses to Hydrogen Peroxide and Nitric Oxide in Human Pericardial Resistance Arteries Stimulated with Endothelin‐1

“…We used this indirect approach because mechanical removal and selective chemical damage of the endothelium proved to be difficult and poorly reproducible in human pericardial resistance arteries. This contrasts with experimental animal resistance arteries that we investigated previously and may be related to the unusual structure of the internal elastic lamina in the pericardial resistance arteries [22]. For a few patients, arterial segments did not contract in response to all three contractile stimuli, but only to two of K + , ET-1 and U46619.…”

“…Selective removal of the endothelium by mechanical or chemical methods without damage to the smooth muscle proved to be difficult and poorly reproducible in these human pericardial resistance arteries. The unusual structure of the internal elastic lamina [22] and the small contractility of the smooth muscle in these vessels (maximal contractility: approximately 1.5 N/m versus 5.0 and 10.0 N/m in rat mesenteric and pig pericardial resistance arteries, respectively [11,22]) may have contributed. Instead, we used pharmacological inhibitors of several established mechanisms of EDR, such as COX, NOS, K Ca 2.3 and K Ca 3.1.…”